Search

Elevated blood glucose is frequently detected early after aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate whether hyperglycemia at admission is associated with mortality in patients with aSAH.In a multicenter observational study of patients with aSAH, we defined normal glycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia as blood glucose of 4.00-6.09 mmol/L, 6.10-7.80 mmol/L, 7.81-10.00 mmol/L, and 10.00 mmol/L, respectively. We performed propensity score matching to obtain the adjusted odds ratios (OR) with 95 % confidence intervals (CI).Of 6771 patients with aSAH, 511(7.5 %) had died in hospital, and hyperglycemia at admission was observed in 4804 (70.9 %). Propensity scores matching analyses indicated that compared with normal glycemia, the odds of in-hospital mortality were slightly lower in patients with mild hyperglycemia (OR 0.89, 95 % CI 0.56-1.40), significantly higher in patients with moderate hyperglycemia (OR 1.90, 95 % CI 1.20-3.01), and in patients with severe hyperglycemia (OR 3.45, 95 % CI 2.15-5.53; P trend 0.001). Long-term survival was worse among patients with hyperglycemia and was proportional to its severity. Similar dose-response associations were evident for poor functional outcomes and major disability. Hyperglycemia was associated with an increased risk of hospital-acquired infections (OR 1.46, 95 % CI 1.29-1.66) and rebleeding (OR 1.58, 95 % CI 1.06-2.35).Among aSAH patients, hyperglycemia at admission was independently associated with increased mortality. Both moderate hyperglycemia and severe hyperglycemia were associated with an increased risk of mortality, but these associations were not seen in mild hyperglycemia (blood glucose 6.10-7.80 mmol/L).

Lactate dehydrogenase (LDH) has been reported to be associated with outcomes after surgery in patients with aneurysmal subarachnoid hemorrhage (aSAH), but it is unclear if this is independent from other biomarkers and across all aSAH treatments. This study aims to assess whether LDH is an independent predictor of mortality in patients with aSAH and test whether the inclusion of LDH in a well-established prediction model can improve discrimination and reclassification.This was a retrospective observational study at a tertiary academic medical center. This study measured baseline LDH levels taken at admission and longitudinal LDH levels (up to a month postadmission) to assess median, max, and trajectory LDH levels. The primary outcome was mortality at 90 days. Multivariable regression analyses were used to evaluate associations between LDH and outcomes. The full original Subarachnoid Hemorrhage International Trialists' (SAHIT) model was used as the reference model.In total, 3524 patients with aSAH were included. LDH at admission was independently associated with mortality at 90 days (quartile 4 vs. 1: odds ratio 1.60; 95% CI 1.08-2.37) and mortality at the longest follow-up (quartile 4 vs. 1: hazard ratio1.72; 95% CI 1.34-2.20). Compared with the SAHIT model, the addition of three LDH (admission, max, and median) levels to the SAHIT model significantly improved the area under the curve and categorical net reclassification improvement for prediction mortality.In patients with aSAH, LDH level is an independent predictor of all-cause mortality. The incorporation of LDH into a well-established prediction model improved the ability to predict the risk of death in patients with aSAH.

As the second most common primary intracranial neoplasms, about 40% of pituitary adenomas (PAs) exhibit aggressive behaviors and resulting in poor patient prognosis. The molecular mechanisms underlying the aggressive behaviors of PAs are not yet fully understood. Biochemical studies have reported that programmed cell death 10 (PDCD10) is a component of the striatin-interacting phosphatase and kinase (STRIPAK) complex and plays a dual role in cancers in a tissue or disease-specific manner. In the present study, we report for the first time that the role of PDCD10 in PAs. Cell proliferation, migration and invasion were either enhanced by overexpressing or inhibited by silencing PDCD10 in PA cells. Moreover, PDCD10 significantly promoted epithelial–mesenchymal transition (EMT) of pituitary adenoma cells. Mechanistically, we showed that the expression of CXCR2, together with phosphorylation levels of AKT and ERK1/2 were regulated by PDCD10. Activation of CXCR2 inversed inactivation of AKT/ERK signal pathways and the tumor-suppressive effects induced by PDCD10 silencing. Finally, the pro-oncogenic effect of PDCD10 was confirmed by in vivo tumor grafting. Taken together, we demonstrate for the first time that PDCD10 can induce aggressive behaviors of PAs by promoting cellular proliferation, migration, invasion and EMT through CXCR2-AKT/ERK signaling axis CA extern

Low serum albumin levels have been identified as a predictor of infectious complications in critically ill patients. However, the association in patients with aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. We aimed to evaluate the prognostic value of hypoalbuminemia using blood samples at admission in patients with aSAH.In a multicenter observational study of patients with aSAH, serum albumin counts were collected on admission. Hypoalbuminemia was defined as a total albumin level 35 g/L. Multivariable logistic regression analyses and propensity score matching were performed to obtain the adjusted odds ratios (ORs) with 95% confidence intervals (CI) for the primary outcome of hospital-acquired infections.A total of 5448 patients were included in the observational cohort study. The odds of hospital-acquired infections were significantly higher in patients with albumin levels 30-34.9 g/L (OR 1.62, 95% CI 1.38-1.90), 25-29.9 g/L (OR 1.97, 95% CI 1.54-2.51), and 24.9 g/L (OR 2.43, 95% CI 1.53-3.86) compared with patients with albumin level ≥ 35 g/L. The odds of hospital-acquired infections with a change in albumin levels from admission to 48-72 h later of lower than - 10 g/L and - 10 to - 5 g/L were 1.67 (95% CI 1.41-1.86) and 1.24 (95% CI 1.05-1.46), respectively, compared with a change in albumin levels of - 5 to 5 g/L.In this large study of matched patients with aSAH, hypoalbuminemia at admission was associated with hospital-acquired infections. A decrease in serum albumin levels within 72 h of admission was associated with higher hospital-acquired infections.

Background: The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral Haemorrhage Trial is an ongoing international, multicentre, stepped wedge, cluster-randomized trial to determine the effectiveness of a goal-directed care bundle (early intensive blood pressure [BP] lowering, glycaemic control, treatment of pyrexia, and reversal of anticoagulation), as compared to standard of care, on patient-centred outcomes after acute intracerebral haemorrhage (ICH). An embedded process evaluation aims to identify factors related to the uptake and implementation of the intervention. Herein, we present the process evaluation results for hospital sites in China. Methods/Design: A mixed methods approach, including surveys, focused group discussions and interviews with clinicians, routine monitoring, and recruitment logs were used to collect data across purposively sampled hospitals. Medical Research Council guidance and normalization process theory were used as theoretical frameworks for design, data analysis, and synthesis. Results: Twenty quantitative surveys were completed with clinicians, and 26 interviews and 2 focus group discussions were conducted during 2019–2020. The care bundle was generally delivered as planned and acceptable by doctors and nurses, but difficulties were reported in achieving the protocol-defined target levels of BP and glycaemic control. Resistance to implementing the care bundle occurred for patients perceived to be at high risk of adverse effects. Common organizational contextual factors that impeded implementation included delayed processes and limited medication supply, while established background care procedures, expertise, and capacity influenced its integration into routine practice. Areas to facilitate implementation included optimizing workflow within available resources, having a dedicated team, and recognizing the potential benefits of the intervention. Conclusions: Varied established care protocols across sites, different levels of background expertise, and lack of staff capacity impeded the integration of goal-directed care bundle into routine practice for ICH patients in China. Ready identification, and efforts to address, these barriers could facilitate uptake of future guideline-recommended interventions for the management of patients with ICH.

BACKGROUND AND PURPOSE We aimed to build a nomogram, based on patients with spontaneous intracerebral hemorrhage (SICH), to predict the probability of mortality and morbidity at 7 days and 90 days, respectively. METHODS We performed a retrospective study, with patients at less than 6 h from ictus admitted to the department of neurosurgery in a single institute, from January 2011 to December 2018. A total of 1036 patients with SICH were included, 486 patients (46.9%) were 47-66 years old at diagnosis, and 711 patients (68.6%) were male. The least absolute shrinkage and section operator method was performed to identify the key adverse factors predicting the outcomes in patients with SICH, and multivariate logistic regression analysis was built on these variables, and then the results were visualized by a nomogram. The discrimination of the prognostic models was measured and compared by means of Harrell's concordance index (C-index), calibration curve, area under the curve (AUC), and decision curve analysis (DCA). RESULTS Multivariate logistic regression analysis revealed that factors affecting 7-day mortality, including the following: age, therapy, Glasgow Coma Scale (GCS) admission, location, ventricle involved, hematoma volume, white blood cell (WBC), uric acid (UA), and L-lactic dehydrogenase (LDH); and factors affecting 90-day mortality, including temperature, therapy, GCS admission, ventricle involved, WBC, international normalized ratio, UA, LDH, and systolic blood pressure. The C-index for the 7-day mortality and 90-day mortality prediction nomogram was 0.9239 (95% CI = 0.9061-0.9416) and 0.9241 (95% CI = 0.9064-0.9418), respectively. The AUC of 7-day mortality was 92.4, as is true of 90-day mortality. The calibration curve and DCA indicated that nomograms in our study had a good prediction ability. For 90-day morbidity, age, marital status, and GCS at 7-day remained statistically significant in multivariate analysis. The C-index for the prediction nomogram was 0.6898 (95% CI = 0.6511-0.7285), and the calibration curve, AUC as well as DCA curve indicated that the nomogram for the prediction of good outcome demonstrated good agreement in this cohort. CONCLUSIONS Nomograms in this study revealed many novel prognostic demographic and laboratory factors, and the individualized quantitative risk estimation by this model would be more practical for treatment management and patient counseling.

The effects of tranexamic acid on spontaneous intracerebral hemorrhage in reducing hematoma expansion and mortality as well as its role in thromboembolic complications and in the improvement of functional outcomes remain substantially uncertain. The objective of this systematic review was to evaluate the efficacy and safety of tranexamic acid in patients with spontaneous intracerebral hemorrhage. Several databases were searched from inception up to 20 June, 2021. We included randomized controlled trials that compared tranexamic acid with placebo or no treatment for the management of intracerebral hemorrhage. The primary outcomes were hematoma expansion and 90-day mortality. The secondary outcomes were hemorrhagic volume change, thromboembolic complications, and functional outcomes. Overall, six trials with 2800 patients were included in this meta-analysis. Tranexamic acid was associated with a reduced risk of hematoma expansion (relative risk 0.87, 95% confidence interval [CI] 0.77–0.99, p = 0.03, I2 = 0%, six trials with 2800 participants) and a lessening of hematoma volume change (mean difference − 1.28, 95% CI − 2.44 to − 0.12; p = 0.03; I2 = 0%, four trials with 2626 participants), without a corresponding higher rate of major thromboembolic complications (relative risk 1.20, 95% CI 0.85–1.69; p = 0.80; I2 = 0%, five trials with 2759 participants). The present analysis also demonstrated that tranexamic acid had no effect on reducing 90-day mortality (relative risk 1.02, 95% CI 0.88–1.19; p = 0.80; I2 = 0%, five trials with 2770 participants). In adults with spontaneous intracerebral hemorrhage, tranexamic acid reduced the risk of intracerebral hemorrhage growth compared with the control. The effects on 90-day mortality remained inconclusive. Further studies should report death within 24 h and death due to bleeding whenever possible.

Background and Purpose: Systemic inflammation is recognized as a hallmark of stroke. We aimed to evaluate the prognostic value of various inflammatory factors using blood at admission in patients with aneurysmal subarachnoid hemorrhage. Methods: In a multicenter observational study of patients with aneurysmal subarachnoid hemorrhage, the counts of neutrophil, platelet, and lymphocyte were collected on admission. Patients were stratified based on neutrophil counts with propensity score matching to minimize confounding. We calculated the adjusted odds ratios with 95% CIs for the primary outcome of in-hospital mortality and hospital-acquired infections. Results: A total of 6041 patients were included in this study and 344(5.7%) of them died in hospital. Propensity score matching analyses indicated that compared with the lower neutrophil counts, higher neutrophil counts were associated with increased risk of in-hospital mortality (odds ratio, 1.53 [95% CI, 1.14–2.06]), hospital-acquired infections (odds ratio, 1.61 [95% CI, 1.38–1.79]), and delayed neurological ischemic deficits (odds ratio, 1.52 [95% CI, 1.09–1.97]). Moreover, out of all the inflammatory factors studied, neutrophil counts demonstrated the highest correlation with in-hospital mortality and hospital-acquired infections. Conclusions: Among patients with aneurysmal subarachnoid hemorrhage, high neutrophil counts at admission were associated with increased mortality and hospital-acquired infections. The neutrophil count is a simple, useful marker with prognostic value in patients with aneurysmal subarachnoid hemorrhage.

Objective: The relationship between smoking and clinical outcomes after aneurysmal subarachnoid hemorrhage (aSAH) is poorly clarified, and current pieces of evidence are inconsistent. The purpose of this multicenter cohort study is therefore to explore the relationship between smoking and mortality as well as several complications after aSAH. Methods: Databases of patient records were from 4 tertiary hospitals. We assessed the impact of tobacco use and tobacco dose (categorized based on smoking index [SI]) on several complication and overall outcome variables. The primary outcome was mortality within the longest follow-up. Logistic models were used to investigate univariate and multivariate relationships between predictors and outcomes. We also developed a propensity score matching for smoking status by using all known confounders. Results: A total of 6,578 patients with aSAH were analyzed. Current smoking and former smoking did not show association with mortality within the longest follow-up (odds ratio [OR], 0.95, 95% confidence interval [CI]: 0.69–1.30, p = 0.726; OR, 0.66, 95% CI: 0.38–1.15, p = 0.139, respectively). In addition, patients who were current smokers showed an independent association with the decreased occurrence of hydrocephalus (OR, 0.60; 95% CI: 0.41–0.88; p = 0.009) after matching all known confounders. We also found moderate smoking (SI between 384 and 625) was associated with reduced mortality in hospital. Conclusions: Our results indicated that in patients with aSAH, current smoking or former smoking was not associated with all-cause mortality up to 7-year follow-up.

RATIONALE AND OBJECTIVES This study aimed to evaluate the value of background parenchymal enhancement (BPE) and diffusion-weighted image (DWI) histogram features in differentiating among different molecular subtypes of breast cancers and investigate the relationship between BPE and DWI features. MATERIALS AND METHODS We prospectively enrolled 142 patients with breast cancer between January and November 2018. All patients underwent breast magnetic resonance imaging before core needle biopsy. The quantitative BPE from dynamic enhanced images and the first-order histogram features extracted from DWI were analyzed. Univariate analysis of variance was used to compare differences in DWI histogram features and BPE characteristics among different molecular subtypes. Spearman test was used to compare the correlation between these imaging indexes. RESULTS A total of 142 patients had 142 lesions, including 17 cases of triple-negative breast cancer, 12 cases of luminal A type breast cancer, 39 cases of luminal B type breast cancer, and 74 cases of human epidermal growth factor receptor 2-positive breast cancer. The apparent diffusion coefficient (ADC) 95th percentile, ADC kurtosis, and BPE were significantly different among 4 subtype groups (P < 0.05), especially between the triple-negative subtype and any other subtype (P < 0.05 in pairwise comparisons). There was a weak but significant correlation between BPE and kurtosis of ADC (r = -0.176, P = 0.036). CONCLUSIONS Diffusion-weighted image histogram features (95th percentile ADC value and kurtosis value of ADC) and BPE features were different in the 4 molecular subtypes of breast cancer, especially in the triple-negative breast cancer subtype. Background parenchymal enhancement was negatively correlated with the kurtosis value of ADC.

Background Tumor-infiltrating lymphocytes (TILs) have become a promising biomarker for assessing tumor immune microenvironment and predicting immunotherapy response. However, the assessment of TILs relies on invasive pathological slides. Methods We retrospectively extracted radiomics features from magnetic resonance imaging (MRI) to develop a radiomic cohort of triple-negative breast cancer (TNBC) (n = 139), among which 116 patients underwent transcriptomic sequencing. This radiomic cohort was randomly divided into the training cohort (n = 98) and validation cohort (n = 41) to develop radiomic signatures to predict the level of TILs through a non-invasive method. Pathologically evaluated TILs in the H&E sections were set as the gold standard. Elastic net and logistic regression were utilized to perform radiomics feature selection and model training, respectively. Transcriptomics was utilized to infer the detailed composition of the tumor microenvironment and to validate the radiomic signatures. Results We selected three radiomics features to develop a TILs-predicting radiomics model, which performed well in the validation cohort (AUC 0.790, 95% confidence interval (CI) 0.638–0.943). Further investigation with transcriptomics verified that tumors with high TILs predicted by radiomics (Rad-TILs) presented activated immune-related pathways, such as antigen processing and presentation, and immune checkpoints pathways. In addition, a hot immune microenvironment, including upregulated T cell infiltration gene signatures, cytokines, costimulators and major histocompatibility complexes (MHCs), as well as more CD8+ T cells, follicular helper T cells and memory B cells, was found in high Rad-TILs tumors. Conclusions Our study demonstrated the feasibility of radiomics model in predicting TILs status and provided a method to make the features interpretable, which will pave the way toward precision medicine for TNBC.

This study aims to construct a Macrophage-Related Gene Prognostic Index (MRGPI) for glioblastoma (GBM) and explore the underlying molecular, metabolic, and immunological features. Based on the GBM dataset from The Cancer Genome Atlas (n = 156), 13 macrophage-related hub genes were identified by weighted gene co-expression network (WGCNA) analysis. 5 prognostic genes screened by Kaplan-Meire (K-M) analysis and Cox regression model were used to construct the MRGPI, including GPR84, NCF2, HK3, LILRB2, and CCL18. Multivariate Cox regression analysis found that the MRGPI was an independent risk factor (HR = 2.81, CI95: 1.13-6.98, p = 0.026), leading to an unfavorable outcome for the MRGPI-high group, which was further validated by 4 validation GBM cohorts (n = 728). Thereafter, the molecular, metabolic, and immune features and the clinical implications of the MRGPI-based groups were comprehensively characterized. Gene set enrichment analysis (GSEA) found that immune-related pathways, including inflammatory and adaptive immune response, and activated eicosanoid metabolic pathways were enriched in the MRGPI-high group. Besides, genes constituting the MRGPI was primarily expressed by monocytes and macrophages at single-cell scope and was associated with the alternative activation of macrophages. Moreover, correlation analysis and receiver operating characteristic (ROC) curves revealed the relevance between the MRGPI with the expression of immune checkpoints and T cell dysfunction. Thus, the responsiveness of samples in the MRGPI-high group to immune checkpoint inhibitors (ICI) was detected by algorithms, including Tumor Immune Dysfunction and Exclusion (TIDE) and Submap. In contrast, the MRGPI-low group had favorable outcome, was less immune active and insensitive to ICI. Together, we have developed a promising biomarker to classify the prognosis, metabolic and immune features for GBM, and provide references for facilitating the personalized application of ICI in GBM.

The pathological implications of tumor-associated macrophages in the glioma microenvironment have been highlighted, while there lacks a gene signature to characterize the functional status and clinical implications of these cells. Comprehensive bioinformatics approaches were employed to develop an M2 macrophage-associated gene signature at bulk-tumor and single-cell levels and explore immunological and metabolic features. Consequently, the PI3K pathway and fatty acid metabolism were correlated with the M2 fraction. Further distilling the pathway members resulted in a leukotriene synthesis-related gene signature (Macro index), including PIK3R5, PIK3R6, ALOX5, ALOX5AP, and ALOX15B, that was primarily expressed by monocytes/macrophages. Increased Macro index predicted IL13-induced macrophages, and was associated with T-cell dysfunction at both transcriptional and epigenetic levels and predicted an unfavorable outcome. Besides, the Macro index was proportional with PAI1 at the protein level, with high levels of the latter suggesting a decreased progression-free interval of glioblastoma. Notably, the monocytes/macrophages in the glioma environment contribute to the expression of immune checkpoints and the Macro index predicts glioma responsiveness to anti-PD1 treatment. Together, our study proposed a leukotriene synthesis-related M2 macrophage gene signature, which may provide insights into the role of these cells in the glioma microenvironment and facilitate individually tailored therapeutic strategies for the disease.

Background Although the characteristics of intracranial aneurysms (IAs) in different age groups have been well documented, they remain relatively unclear in elderly patients due to a lack of large sample studies. Methods Data from IA patients aged more than 70 years who were treated in our centre from January 2016 to January 2020 were retrospectively collected. Results A total of 290 elderly patients (75.9% female) with a mean age of 74.0 ± 4.7 years were analysed. Rupture occurred in 60.7% of patients, 38.6% of whom presented with meningeal irritation, and seizures were noted in 2.3%. A total of 48.9% of the patients with ruptured IAs had initial symptoms presenting with slow development, and the mean delay from ictus was prolonged to 264.2 ± 914.0 hours. In addition, 61.9% of the patients with ruptured IAs had lesions with a maximum diameter of less than 5 mm. A total of 30.3% of the patients had multiple aneurysms, 35.5% had aneurysms with irregular shapes and 54.8% had cerebrovascular atherosclerotic stenosis (CAS). Pulmonary infection (n = 138, 47.6%), hydrocephalus (n = 72, 24.8%), and thrombosis (n = 35, 12.1%) were common complications during hospitalization. By the end of the 1-year follow-up, 22.1% of the patients had unfavourable clinical outcomes, and the mortality rate was 23.4%. Conclusions Several characteristics regarding IAs in elderly patients were reported, including an obvious female predominance; mild, slow initial symptom development causing prolonged admission delay; a low incidence of meningeal irritation and seizures due to decreased electrophysiological activity of the neurons; increased percentages of CAS, multiple aneurysms, and aneurysms with daughter sacs causing a high risk of rupture even for small lesions; a high risk of complications during hospitalization; and relatively poor clinical outcomes.

BackgroundIntracranial non-branching site blood blister-like aneurysms (BBA) are extremely rare and vicious. Their etiology remains elusive, and no molecular study has been carried out to reveal its pathogenic relevance to intracranial atherosclerosis. To investigate its transcriptomic landscape and underlying potential pathogenesis, we performed single-cell RNA sequencing with extensive pathological validation.MethodsIn total, 12,245 cells were recovered for single-cell RNA sequencing analysis from 1 BBA and 2 saccular intracranial aneurysms (IAs). Unbiased clustering using Seurat-based pipeline was used for cellular landscape profiling. Cellchat was used to understand intracellular communications. Furthermore, 10 BBAs and 30 IAs were retrospectively collected for pathological validations like scanning electron microscopy, H&E stain, Masson stain, Verhoeff Van Gielson stain, and immunofluorescence.ResultsSingle-cell transcriptome profiled 14 total subclusters in 6 major groups, namely, 6 monocyte/macrophage clusters, 2 T&NK clusters, 3 vascular smooth muscle cell (VSMC) clusters, 1 dendritic cell, 1 B cell, and 1 endothelial cell cluster. The only mural cell identified in BBAs was VSMC-2 cluster, while mural cells in IAs comprise most clusters of VSMCs and endothelial cells. Upregulated genes in BBA-derived VSMCs are related to arterial mineralization and atherosclerosis, such as PTX3, SPP1, LOX, etc., whereas vasodilation and physiological regulatory genes such as MGP, ACTA2, and MYL9 were conversely enriched in conventional IA-derived VSMCs. Immune cells in the BBA were predominantly macrophages, with a low fraction of T&NK cells, while conventional IAs had a higher percentage of T&NK. Gene enrichment analysis suggested that macrophages in BBA were highly enriched in lipid metabolism as well as atherosclerosis. Ligand–receptor interaction suggested that secretory phosphoprotein 1 (also known as osteopontin) played a major role in mediating the intracellular communication between VSMC and macrophages, especially in BBA. Pathological experiments corroborate with the bioinformatic findings and further characterized BBAs as a thin-walled thrombotic aneurysm with severe atherosclerotic lesions, where ApoE+ macrophages and OPN+ mural cells are intimately involved in the inflammation process.ConclusionsThe preexisting intracranial atherosclerosis might predispose the parent artery to the pathogenic occurrence of BBAs. These data shed light on the pathophysiology of intracranial aneurysms and might assist in the further resolution of the complexity in aneurysm pathogenesis.

Objective The relative effects of monoclonal antibody against calcitonin gene-related peptide (CGRP) or its receptor for adult migraine patients with prior treatment failure remains uncertain. Therefore, this study systematically assessed the comparative effectiveness of different CGRP binding monoclonal antibodies (mAbs) for these patients. Methods Several online databases including Ovid MEDILNE, Ovid EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to June 15, 2022. We included randomized clinical trials (RCT) of adult migraine patients with previous treatment failure that assessed any CGRP monoclonal antibody. The primary efficacy outcome was change in monthly migraine days (MMDs), and the primary safety outcome was treatment-emergent adverse events (TEAEs). Results Overall, seven studies totaling 3, 052 patients were included. Three-node analysis showed that CGRP mAbs was superior to CGRP receptor mAbs in reducing MMDs (MD: -1.55, 95% CrI: − 2.43 to − 0.44) and improving at least 50% response rates (RR: 1.52, 95% CrI: 1.04 to 2.21). Nine-node analysis showed galcanezumab 240 mg ranked first in reducing MMDs (MD -4.40, 95% CrI − 7.60 to − 1.19) and improving 50% response rates (RR: 4.18, 95% CrI: 2.63 to 6.67). Moreover, treatment with fremanezumab or eptinezumab 300 mg provides a significant advantage over erenumab 140 mg regarding an improved response rate of at least 50%. The analysis did not show difference in incidences of TEAEs and serious adverse events in any of the comparisons. Conclusions It appears that CGRP mAbs, especially galcanezumab 240 mg, monthly fremanezumab, and eptinezumab 300 mg, seem to be the best choice for the treatment of migraine patients with previous treatment failures. This finding also calls for future research that examine the associations between these medications in migraine therapy among the same patient group to testify the present findings.

Until now, it has remained difficult for doctors to make an informative decision as to which concentration of hypertonic saline (HTS) is more beneficial for patients with traumatic brain injury (TBI). We therefore investigate the effect of different concentrations of hypertonic saline on mortality and ICP lowering efficacy in this group of patients.Several databases including Ovid MEDLINE, Ovid EMBASE, PubMed, and Cochrane Central Register of Controlled Trials were searched comprehensively from inception to February 28, 2022. We only included RCTs that compared HTS with different concentrations and mannitol in adult patients with TBI. The main outcome was mortality from any cause. We reported relative risks (RR) and 95% confidence intervals (CIs) from direct meta-analysis and 95% credible intervals (CrIs) from network meta-analysis.Overall, 13 trials containing 593 patients were included in this study. Direct analysis revealed that HTS was associated with decreased risk of all-cause mortality (RR, 1.29; 95% CI: 1.08 to 1.54). In the network meta-analysis, 5% HTS was associated with a significant decrease in all-cause mortality compared with mannitol (RR 0.34, 95% CrI: 0.14 to 0.72). We also found 7.5% HTS was associated with a significant increase in all-cause mortality compared with 5% HTS (RR, 2.87; 95% CrI: 1.00 to 8.99).Among patients with TBI, the application of 5% HTS was associated with decreased all-cause mortality compared with mannitol and other concentration. Treatments with 10% and 15% HTS was more likely to decrease ICP compared with other fluids. More trials are needed to verify the current findings.

Treating blood blister-like aneurysms (BBA) is a major neurosurgical challenge. Whether endovascular repair serves as a better strategy than microsurgery remains controversial. We aim to perform a propensity score-matched (PSM) retrospective study to analyze the short-term outcome in BBA patients who received microsurgery and endovascular treatment. One hundred fifty-five eligible patients with internal carotid artery BBA were retrospectively collected with demographic and angiographic baseline in a single center. Three-month outcome and adverse events were set as outcome endpoints. PSM was used to match the microsurgery and endovascular group. Matching effect was evaluated by distribution variation analysis and love plot. The outcome of neurosurgery and endovascular treatment was then compared before and after PSM. Better WFNS levels (p = .017) and modified Fisher grade (p = .027) were noted in endovascular group before matching. Other baseline including angiographic features were comparable between two groups. Before matching, the 3-month outcome of endovascular repair surgery was more favorable than microsurgery (p .0001). The occurrence of adverse events was also higher in the microsurgery group (p = .0079). In PSM-adjusted groups, the superior outcome effect of endovascular treatment still existed but with a reduced significance (p = .004). Similar trend was also observed in the adverse event rate (p = .038). Fatality rate was comparable between two adjusted groups regardless of PSM adjustment. Endovascular surgery of BBAs exhibits overall more favorable short-term outcome regardless of PSM matching. Microsurgery does not cause a higher fatality rate, hence it could be considered a salvage plan for those high-grade BBA patients.

The use of prophylactic anticonvulsants among patients with subarachnoid hemorrhage (SAH) is controversial. We sought to assess the effectiveness of different durations of prophylactic antiepileptic drug (AED) use among SAH patients. We searched the MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases until March 1, 2020. Randomized controlled trials or observational studies comparing different durations or different drugs were selected. The primary outcome was poor clinical outcomes. The secondary outcome was in-hospital seizure. Bayesian network meta-analysis was also performed to indirectly compare the effectiveness of different prophylaxes. A total of 5 papers were included. Three studies with a total of 959 patients were included in the analysis of the primary outcome; the results showed that long-term exposure to prophylactic AEDs (more than 3 days) led to poor clinical outcomes (OR 1.55; 95% CI 1.01–2.39; p = 0.045). Four studies with 1024 patients were included in the analysis of the secondary outcome; the results showed no association between the duration of prophylactic AED use and the occurrence of in-hospital seizures (OR 0.62; 95% CI 0.18–2.15; p = 0.447). In the network meta-analysis, no significant difference was found among the four different prophylaxes. Our findings suggested that, when compared with the short-term use, the long-term use of prophylactic AEDs in SAH patients has a similar effect on in-hospital seizure prevention but is associated with poor clinical outcomes. However, these findings were based on a small number of available studies with obvious heterogeneity in study design and different prescription regimens. Further well-designed studies are warranted to elucidate these questions.

Background Radiomics plays an important role in the field of oncology. Few studies have focused on the identification of factors that may influence the classification performance of radiomics models. The goal of this study was to use contrast-enhanced mammography (CEM) images to identify factors that may potentially influence the performance of radiomics models in diagnosing breast lesions. Methods A total of 157 women with 161 breast lesions were included. Least absolute shrinkage and selection operator (LASSO) regression and the random forest (RF) algorithm were employed to construct radiomics models. The classification result for each lesion was obtained by using 100 rounds of five-fold cross-validation. The image features interpreted by the radiologists were used in the exploratory factor analyses. Univariate and multivariate analyses were performed to determine the association between the image features and misclassification. Additional exploratory analyses were performed to examine the findings. Results Among the lesions misclassified by both LASSO and RF ≥ 20% of the iterations in the cross-validation and those misclassified by both algorithms ≤5% of the iterations, univariate analysis showed that larger lesion size and the presence of rim artifacts and/or ripple artifacts were associated with more misclassifications among benign lesions, and smaller lesion size was associated with more misclassifications among malignant lesions (all p p = 0.002) and the presence of air trapping artifacts (OR = 35.568, p = 0.025) were factors that may lead to misclassification among malignant lesions. Additional exploratory analyses showed that benign lesions with rim artifacts and small malignant lesions ( Conclusions Lesion size and artifacts in CEM images may affect the diagnostic performance of radiomics models. The classification results for lesions presenting with certain factors may be less reliable.

IntroductionSeizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping.Methods and analysisIn this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0–2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat.Ethics and disseminationThis study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR.Trial registration numberChiCTR.org identifier: ChiCTR2100050161.

Test of different myocardial biomarkers is commonly arranged in patients with aneurysmal subarachnoid hemorrhage (aSAH). We sought to figure out whether different myocardial biomarkers' elevation is related to characteristics of ruptured aneurysms and patients' clinical outcomes. Patients with aSAH admitted in the Neurosurgery Department of West China Hospital from September 2019 to March 2020 were screened. Those who have one clear responsible aneurysm and met inclusion criteria were included. Clinical characteristics, site and size of the aneurysm, modified Fisher scale, troponin T (TPN-T), creatine kinase MB (CK-MB), and myoglobin (Myo) levels at admission, clinical outcomes (3-month mRS) were collected and compared. The study included 124 patients. After multivariate logistic regression, Hunt & Hess grade (per unit grade, OR 1.68, 95% CI 1.14–2.49), the size of ruptured aneurysm (equal to or more than 7 mm, OR 3.07, 95% CI 1.32–7.10) was highly predictive of myocardial biomarker elevation. All three biomarkers (TPN-T, CK-MB, Myo) were associated with unfavorable prognoses. Higher mortality (37.2% vs. 18.6%, P = 0.036) and a lower rate of good outcomes (41.9% vs. 71.2%, P = 0.003) were observed in patients with any positive myocardial biomarkers at admission. The clinical outcomes of patients with positive troponin T and negative creatine kinase MB were especially unfavorable. Our study demonstrates that the degree of neurological injury and size of ruptured aneurysm are strong predictors of myocardial biomarkers elevation, the site of ruptured aneurysm may not be associated with heart injury after SAH. The outcomes of patients with different combinations of abnormal biomarker levels may have significant differences and deserve further study.

We aimed to investigate prognostic factors and outcomes of malignant meningioma and to construct a nomogram model of survival.Patients with malignant meningioma were collected from the Surveillance, Epidemiology, and End Results database. The nomogram was developed for the 3-, 5-, and 8-year prediction of overall survival (OS) and cancer-specific survival (CSS). Harrell's concordance index (C-index) and decision curve analysis (DCA) were used to verify the predicted effect of the nomogram.Between 1998 and 2016, 806 adult patients with histologically confirmed malignant meningioma were included. The mean age at diagnosis was 61.0 years (median 61.0 years), with a range of 19-104 years. Univariate analysis revealed that male gender, distant metastasis, and age ≥ 80 years as significant adverse factors for OS and CSS. These factors remained significance in the multivariate analysis. The nomogram demonstrated satisfactory discrimination, with a C-index value of 0.663 for OS and 0.654 for CSS, respectively. For both OS and CSS, the DCA curves indicated that the nomogram model performed better than other clinical variables.Older age, male gender, distant metastasis, and radiotherapy were significantly related to poor prognosis; and extent of resection did not affect survival.

Background The purpose of this study was to introduce the arthroscopic internal drainage with anterior-anteromedial approach for the treatment of popliteal cysts in children. To compare its clinical efficacy with open surgery. Methods This was a retrospective case–control study of 102 patients diagnosed with popliteal cysts from January 2018 to February 2020 who received surgery. The study included 27 cases with minimally invasive group (MI group) and 75 cases with open surgery group (OS group). The MI group included 21 males and 6 females, age 6.71 ± 2.16 years who received arthroscopic internal drainage of the cysts to adequately widen the valve opening between the cyst and the articular cavity, excised the fibrous diaphragm without complete excision of the cyst wall. The OS group included 57 males and 18 females, age 6.21 ± 1.67 years who received open excision. The clinical parameters regarding the preoperative characteristics and surgical results were compared. Ultrasound or MRI was used to identify the recurrence of the popliteal cysts. Rauschning-Lindgren grade was recorded to evaluate the clinical outcome. Results All patients were followed up for at least 24 months. There were no significant differences between the two groups in age, gender, left and right sides, disease time, cyst size, length of hospitalization, preoperative Rauschning-Lindgren grade (p > 0.05). At the last follow-up, the preoperative and postoperative Rauschning-Lindgren grade was improved in both groups. Compared with the OS group, operation time was significantly shortened in the MI group (28.89 ± 4.51 min vs 52.96 ± 29.72 min, p p p = 0.018). No postoperative complications occurred during the follow-up period. Conclusions Compared with open excision, the treatment of popliteal cyst in children by arthroscopic internal drainage to expand the articular cavity and eliminate the “one-way valve” mechanism between the cyst and the articular cavity exhibits better clinical outcomes and significantly reduces the recurrence rate, which is worthy of further clinical promotion.

Gliosarcoma (GSM) is a rare central nervous system tumor. Clinical management of it is similar to glioblastoma (GBM). However, due to a few comparative studies exist, uncertainty and disagreements remain in the literatures. To assess the available evidence on the value of different treatments and to carry out an up-to-date evaluation to summarize the evidence for the optimal treatment in GSM patients. Free words were used to search for the relevant studies without language limitations in electronic databases including PubMed, Ovid EMBASE, Cochrane Central Register of Controlled Trials from inception to September 15, 2019. Pooled hazard ratio (HR) with 95% confidence interval (CI) were calculated using a random-effects model. The main endpoint was all-cause mortality. Overall, 10 studies published between 2008 and 2018 including 803 patients were selected for the meta-analysis. Temozolomide (TMZ)-dominated chemotherapy was associated with a reduced risk of overall survival (OS), with HR 0.49 (95% CI 0.37-0.66). The pooled HR of OS was 0.40 (95% CI 0.29-0.56) between radiotherapy and without radiotherapy. The pooled HR (0.52, 95% CI 0.32-0.85) indicated gross total resection (GTR) had a positive impact on OS in GSM. In patients with GSM, survival benefits as currently performed are associated with TMZ-dominated chemotherapy and high-dose radiotherapy. Our systematic review and meta-analysis also demonstrate GTR is associated with a reduction in all-cause mortality in patients with primary GSM.

To evaluate whether the postoperative neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker for patients with intracerebral hemorrhage (ICH) undergoing surgical hematoma evacuation.This retrospective cohort study was conducted to identify patients with ICH who underwent hematoma evacuation between January 2013 and December 2018. Data on demographics, clinical features, laboratory tests (admission and postoperative), and imaging information were collected. The associations between variables and 30-day mortality were assessed by multivariable logistic regression analysis. The predictive power of independent predictors was evaluated by receiver operating characteristic (ROC) curve analysis.A total of 380 patients were included. Multivariable analysis identified admission Glasgow Coma Scale score (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.53-0.70; P0.001) and initial hematoma volume (OR, 1.01; 95% CI, 1.01-1.02; P = 0.022) were independently associated with 30-day mortality. With regard to laboratory biomarkers, postoperative NLR (OR, 1.04; 95% CI, 1.01-1.08; P = 0.014) was independently correlated with 30-day death, but admission NLR (OR, 1.00; 95% CI, 0.97-1.03; P = 0.944) was not. The best predictive cutoff point of 12.97 for postoperative NLR (area under the ROC curve, 0.606; P = 0.006) for predicting 30-day mortality was determined by ROC analysis.In patients with ICH undergoing hematoma evacuation, admission Glasgow Coma Scale score, initial hematoma volume, and postoperative NLR were independently associated with 30-day mortality. Postoperative NLR may be a prognostic marker in surgical ICH patients, and future studies are needed to confirm this finding.

Background We established a radiogenomic model to predict pathological complete response (pCR) in triple-negative breast cancer (TNBC) and explored the association between high-frequency mutations and drug resistance. Methods From April 2018 to September 2019, 112 patients who had received neoadjuvant chemotherapy were included. We randomly split the study population into training and validation sets (2:1 ratio). Contrast-enhanced magnetic resonance imaging scans were obtained at baseline and after two cycles of treatment and were used to extract quantitative radiomic features and to construct two radiomics-only models using a light gradient boosting machine. By incorporating the variant allele frequency features obtained from baseline core tissues, a radiogenomic model was constructed to predict pCR. Additionally, we explored the association between recurrent mutations and drug resistance. Results The two radiomics-only models showed similar performance with AUCs of 0.71 and 0.73 (p = 0.55). The radiogenomic model had a higher predictive ability than the radiomics-only model in the validation set (p = 0.04), with a corresponding AUC of 0.87 (0.73–0.91). Two highly frequent mutations were selected after comparing the mutation sites of pCR and non-pCR populations. The MED23 mutation p.P394H caused epirubicin resistance in vitro (p p p Conclusions The proposed radiogenomic model has the potential to accurately predict pCR in TNBC patients. Epirubicin resistance after MED23 p.P394H mutation might be affected by HR repair through regulation of the p-ATM-γ-H2A.X-p-CHK2 pathway.

Background: Homologous recombination (HR) is a key pathway in DNA double-strand damage repair. HR deficiency (HRD) more commonly occurs in triple-negative breast cancers (TNBCs) than in other breast cancer subtypes. Several clinical trials have demonstrated the value of HRD in stratifying breast cancer patients into distinct response groups to poly ADP ribose polymerase (PARP) inhibitors and chemotherapy.Methods: We retrospectively collected TNBC samples to establish a multiomics cohort (n=343) to explore the biological and phenotypic mechanisms underlying the better prognosis of patients with high HRD scores. The HRD score was calculated using the sum of the telomeric allelic imbalance (TAI) score, loss of heterozygosity (LOH) score and large-scale state transition (LST) score. Gene set enrichment analysis (GSEA) were conducted to reveal underlying pathways of low HRD score patients. Radiomics model were established to predict HRD score in a noninvasive method.Results: Multivariable Cox analysis revealed the independent prognostic value of a low HRD score (hazard ratio, 2.20, 95% confidence interval, 1.05 to 4.59, p=0.04). Furthermore, amino acid and lipid metabolism pathways were highly enriched in tumors with low HRD scores, which was also demonstrated by differentially abundant metabolite analysis. A noninvasive radiomics method was developed to predict HRD status and performed well in the independent validation cohort (support vector machine model: area under the curve (AUC), 0.739, sensitivity, 0.571, and specificity, 0.824; logistic regression model: AUC, 0.695, sensitivity, 0.571, and specificity, 0.882).Conclusions: In conclusion, we revealed the prognostic value of the HRD score, predicted HRD status with noninvasive radiomics features and preliminarily explored druggable targets in TNBC patients with low HRD scores.

Triple-negative breast cancer (TNBC) is a subset of breast cancer with an adverse prognosis and significant tumor heterogeneity. Here, we extract quantitative radiomic features from contrast-enhanced magnetic resonance images to construct a breast cancer radiomic dataset (n = 860) and a TNBC radiogenomic dataset (n = 202). We develop and validate radiomic signatures that can fairly differentiate TNBC from other breast cancer subtypes and distinguish molecular subtypes within TNBC. A radiomic feature that captures peritumoral heterogeneity is determined to be a prognostic factor for recurrence-free survival (p = 0.01) and overall survival (p = 0.004) in TNBC. Combined with the established matching TNBC transcriptomic and metabolomic data, we demonstrate that peritumoral heterogeneity is associated with immune suppression and upregulated fatty acid synthesis in tumor samples. Collectively, this multi-omic dataset serves as a useful public resource to promote precise subtyping of TNBC and helps to understand the biological significance of radiomics.

The adverse health effects of household air pollution have been widely explored, but few studies have evaluated the effects of household air pollution on the risk of cardiometabolic multimorbidity (CMM), a pressing public health concern worldwide. Thus, we aimed to investigate whether exposure to household use of polluting fuels is associated with morbid CMM and, if so, whether a healthy lifestyle could mitigate this association.In this prospective, nationwide representative cohort of the China Health and Retirement Longitudinal Study (CHARLS), participants free of CMM (defined as the coexistence of 2 or more of the following: heart disease, stroke, and diabetes or high blood sugar) were included in 2011-2012 and followed for CMM incidence until 2018. Household air pollution was measured as the use of solid fuels for cooking and heating. The healthy lifestyle score was determined by six factors, physical activity, smoking, body mass index, total cholesterol, blood glucose, and blood pressure, and categorized into three groups (unhealthy, 0-1 factors; intermediate, 2-4; and healthy, 5-6). Cox proportional hazards models investigated associations between household air pollution and incident CMM. The potential modifier effect of a healthy lifestyle score was tested through stratified analyses.Among 7125 eligible participants, 239 incident cases of CMM were identified over a median follow-up of 7.0 years. After adjustment for potential confounders, the use of solid household fuels for heating was associated with more significant hazards of CMM (adjusted hazard ratio [HR] 1.71, 95 % confidence interval [CI] 1.28 to 2.28), while use for cooking (HR, 1.14; 95 % CI, 0.85 to 1.52) was not. Compared with participants in the unhealthy group, those in the healthy and intermediate groups had considerably lower CMM risk, with adjusted HRs (95 % CI) of 0.17 (0.09 to 0.31) and 0.39 (0.29 to 0.53), respectively, regardless of the household air pollution category. Importantly, when participants adhered to a healthy lifestyle, exposure to household air pollution was no longer significantly associated with a higher risk of CMM (adjusted HR 1.77, 95 % CI 0.51 to 6.12; P = 0.369).Household usage of polluting fuels was significantly associated with a higher risk of CMM, and adherence to a healthy lifestyle may mitigate this adverse effect. From a broader perspective, our findings underscore the importance of public health policies and interventions targeting multiple exposures (air pollution, physical activity, smoking, etc.) in enhancing the prevention of detrimental cardiometabolic health effect.

Background: Primary intraventricular hemorrhage (PIVH) is a rare type of Intracerebral Hemorrhage (ICH), which is poorly understood. This study aimed to investigate gender differences in patients' characteristics, management and outcome at discharge and 90 days after PIVH. Methods: Consecutive patients with PIVH from a single center in China were enrolled over a 7- year period. Gender differences in demographics, risk factors, etiological subtypes, treatment, and outcomes were examined. The logistic regression models were used in the study to identify the predictors of poor outcome. Results: In total, 174 patients were analyzed, and 77 (44.3%) of them were women. Women with PIVH were younger (p = 0.047), with lower systolic and diastolic blood pressure (p = 0.02 and p = 0.004, respectively). They had more cases caused by Moyamoya disease (p = 0.038). There were fewer patients with hypertension (p = 0.008), smoking (p＜0.001), chronic alcoholism (p＜0.001), harbored lower hemoglobin (p＜0.001) and Absolute Monocyte Count (AMC) (p = 0.04) at admission compared with men. There were no differences between female and male patients regarding the mortality and poor outcome in the multivariable-adjusted models ((OR = 0.57; 95% CI, 0.15-2.14) and (OR = 0.86; 95% CI, 0.32-2.37), respectively). In subgroup analysis after adjustment, the gender specific independent predictors for unfavorable outcome were higher with a Graeb score (OR = 1.78; 95% CI, 1.01-3.13) or AMC (OR = 9.66; 95% CI, 1.20-12.87) in women, and lower Glasgow coma scale (GCS) score (OR = 0.64; 95% CI, 0.47-0.87) or acute hydrocephalus (OR = 0.17; 95% CI, 0.03-0.86) in men. Conclusions: Women with PIVH exhibit some distinctive baseline features compared with men. The gender difference of the PIVH does not appear to affect the neurological outcome. The predictors of poor outcomes are Graeb score and AMC in women and GCS score and acute hydrocephalus in men.

Blood blister-like aneurysms (BBAs) are extremely rare aneurysms. They are predisposed to preoperative rerupture with a high case-fatality rate. Here, we attempt to interrogate the distinct clinicopathology and the histological basis underlying its clinical rerupture.Three middle meningeal arteries, 11 BBA (5 reruptured, 6 non-rerupture) and 19 saccular aneurysm samples were obtained for histopathological investigation. Three reruptured BBAs, 3 non-reruptured BBAs and 6 saccular (3 ruptured, 3 unruptured) aneurysms were obtained for quantitative flow cytometry analysis.Compared with true saccular aneurysms, the BBA aneurysm wall lacks arterial stroma cells including CD31+ endothelial cells and α-SMA + smooth muscle cells. Only fibroblasts and adventitial collagen were observed in the BBA aneurysm wall. Meanwhile, BBAs were enriched with infiltrated inflammatory cells, especially polarized macrophages. Based on the rerupture status, those reruptured BBAs showed drastically reduced fibroblasts and adventitia collagen. Moreover, M2-polarized macrophages were observed dominant in BBAs and exhibit repairing cellular functions based on their interplays with arterial fibroblasts. Reduced M2 macrophages and arterial tissue repairing modulation may be responsible for the decreasing collagen synthesis and fibrosis repairment, which potentially dampens the aneurysm integrity and induces BBA aneurysm reruputre.BBAs poses histopathological features of occult pseudoaneurysms or dissecting aneurysms. Reduced M2 macrophages and adventitia collagen may dampen the structural integrity of BBAs and induce preoperative rerupture.

Background Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. Methods INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. Discussion As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established. Trial registration ClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017

Background Radiogenomics explores the association between imaging features and genomic assays to uncover relevant prognostic features; however, the prognostic implications of the derived signatures remain unclear. Purpose To identify preoperative radiogenomic signatures of estrogen receptor-positive breast cancer associated with the Oncotype DX recurrence score (RS) and to evaluate whether they are biomarkers for survival and responses to neoadjuvant chemotherapy (NACT). Materials and Methods In this retrospective multicohort study, three data sets were analyzed. The radiogenomic development data set, with preoperative dynamic contrast-enhanced MRI and RS data obtained between January 2016 and October 2019 was used to identify radiogenomic signatures. Prognostic implications of the imaging signatures were assessed by measuring overall survival and recurrence-free survival in the prognostic assessment data set using a multivariable Cox proportional hazards model. The therapeutic implication of the radiogenomic signatures was evaluated by determining their ability to predict the response to NACT using the treatment assessment data set obtained between August 2015 and March 2019. Prediction performance was estimated by using the area under the receiver operating characteristic curve (AUC). Results The final cohorts included a radiogenomic development data set with 130 women (mean age, 52 years ± 10 [standard deviation]), a prognostic assessment data set with 116 women (mean age, 48 years ± 9), and a treatment assessment data set with 135 women (mean age, 50 years ± 11). Radiogenomic signatures (n = 11) of texture and morphologic and statistical features were identified to generate the predicted RS (R2 = 0.33, P < .001). A predicted RS greater than 29.9 was associated with poor overall and recurrence-free survival (P = .001 and P = .007, respectively); predicted RS was greater in women with a good NACT response (30.51 ± 6.92 vs 27.35 ± 4.04 [responders vs nonresponders], P = .001). By combining the predicted RS and complementary features, the model achieved improved performance in prediction of the NACT response (AUC, 0.85; P < .001). Conclusion Radiogenomic signatures associated with genomic assays provide markers of prognosis and treatment in estrogen receptor-positive breast cancer. © RSNA, 2021 Online supplemental material is available for this article.

Background To date, it remains challenging for clinicians to make informed decisions about which dosage of erenumab is more effective for treating adult patients with migraine. Thus, we sought to examine the safety and efficacy of different doses of erenumab in this group of patients. Methods We searched several databases from inception to May 31, 2021, irrespective of language. We included only RCTs that compared erenumab 70 mg, erenumab 140 mg, and placebo in migraine patients. The primary efficacy outcome was change in monthly migraine days (MMDs). The primary safety outcome was defined as treatment-emergent adverse events (TEAEs). We reported relative risks (RRs) with 95% credible intervals (CrIs) from the analysis. Results Overall, eight trials comprising 4281 participants were included in this study. Network meta-analysis showed that both erenumab 70 mg (MD: - 1.43, 95% CrI: - 1.71 to - 1.16) and erenumab 140 mg (MD: - 1.78, 95% CrI: - 2.21 to - 1.45) were associated with decreased MMDs. Also, erenumab 140 mg was associated with significantly lower MMDs than erenumab 70 mg (MD: - 0.34, 95% CrI: - 0.68 to - 0.01). In terms of primary safety outcome, neither erenumab 70 mg (RR: 0.98, 95% CrI: 0.92 to 1.05) nor erenumab 140 mg (RR: 0.99, 95% CrI: 0.91 to 1.07) was associated with increased risk of TEAEs. Conclusions The results from this study suggested erenumab 140 mg might provide better efficacy than 70 mg among adult patients with migraine, without increasing TEAEs. Future elaborated RCTs with a larger number of participants are warranted to validate these discoveries.

In clinical work, the magnetic resonance imaging markers of cerebral small vessel disease (CSVD) are frequently observed in moyamoya disease (MMD), but the clinical significance of these markers in MMD remains unclear. This study aimed to fill this gap and systematically investigate its clinical significance. In this retrospective cohort study, we screened all adult patients with MMD hospitalized from January 2016 to January 2020 and collected their baseline clinical and imaging information. Univariate and multivariate logistic regression analyses were then performed to determine which imaging markers were independently associated with MMD characteristics, including cerebrovascular morphology, cerebral hemodynamics, cerebrovascular events, and postoperative collateral formation (PCF). A total of 312 cerebral hemispheres images were collected from the 156 patients with MMD. Using multivariate logistic regression analysis, the following results were generated: (1) The presence of lacunes (OR, 2.094; 95% CI, 1.109-3.955; p = 0.023) and severe white matter hyperintensities (WMH) (OR, 3.204; 95% CI, 1.742-5.892; p 0.001) were associated with a Suzuki stage ≥ IV; (2) the presence of lacunes (OR, 6.939; 95% CI, 3.384-14.230; p 0.001), higher numbers of enlarged perivascular spaces in centrum semiovale (CSO-EPVS) (OR, 1.046; 95% CI, 1.024-1.067; p 0.001), and severe WMH (OR, 2.764; 95% CI, 1.463-5.223; p = 0.002) were associated with the reduced regional cerebral blood flow; (3) the presence of lacunes (OR, 12.570; 95% CI, 2.893-54.624; p = 0.001), higher numbers of CSO-EPVS (OR, 1.103; 95% CI, 1.058-1.150; p 0.001), and severe WMH (OR, 5.982; 95% CI, 1.727-20.716; p = 0.005) were associated with ischemic cerebrovascular events; (4) the higher number of CSO-EPVS (OR, 1.077; 95% CI, 1.026-1.131; p = 0.003) was associated with good PCF. The lacunes, WMH, and CSO-EPVS were independently associated with these MMD characteristics. In conclusion, this study provided a novel and potential framework for the practical assessment of MMD by magnetic resonance imaging.

Background and Purpose: Chronic liver disease (CLD) is a risk factor for increased morbidity and mortality in acutely ill patients. For patients with aneurysmal subarachnoid hemorrhage (aSAH), the association between CLD and mortality remains unknown. Methods: In this retrospective cohort study, we analyzed consecutive aSAH patients admitted to the West China Hospital between 2009 and 2019. The primary outcome was in-hospital all-cause mortality. Results: This study included 6228 cases of aSAH, 489 (7.9%) of whom also had CLD. In a propensity-matched analysis, CLD was associated with increased mortality in patients with aSAH compared with non-CLD (odds ratio, 2.04 [95% CI, 1.43–2.92]). In aSAH patients with CLD, a high Model for End-Stage Liver Disease score was still associated with an increased odds of mortality. Conclusions: Among aSAH patients, CLD was associated with increased mortality compared with non-CLD. Among aSAH patients with CLD, a higher Model for End-Stage Liver Disease score was associated with an increased odds of mortality.

Background: Pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) with skull base extension is a rare entity. Here, we summarize the clinical features, treatments, and outcomes of PVNS of the TMJ with skull base extension in a large case series. Methods: We reviewed the clinical information relating to patients diagnosed with PVNS of the TMJ with skull base extension information of patients in our center between 2011 and 2020. Results: We reviewed 10 patients (4 males and 6 females). All cases had presented with a unilateral lesion extending the middle skull base. PVNS of the TMJ with skull base extension occurred on the left side in 6 patients (60%) and on the right side in 4 patients (40%). Of the 10 patients, pain and mass were the most prevalent symptoms. All patients received surgery and no recurrence was seen after 35.90±25.35 months follow-up. Conclusion: Despite destructive biological behavior, surgery can achieve an excellent outcome for patients with PVNS of the TMJ with skull base extension. An en bloc resection may prevent recurrence and provide long-term relief. Radiotherapy may be reserved for subtotal excision and recurrent lesions but require further investigation.

IntroductionVentriculoperitoneal shunt (VPS) remains the most widely used methods to treat communicating hydrocephalus. More recently, lumboperitoneal shunt (LPS) has been suggested as a reasonable option in some studies. However, there is lack of high-quality studies comparing these two techniques in order to certain the benefits and harms to use one of these two methods. The purpose of the current study is to determine the effectiveness and safety of the LPS versus the VPS in patients with communicating hydrocephalus.Methods and analysisAll eligible patients aged 18–90 years with communicating hydrocephalus will be recruited and then randomly allocated into LPS or VPS group in a ratio of 1:1. All patients will be analysed before shunt insertion, at the time of discharge, 1 month, 6 months, 12 months and 24 months postoperatively. The primary outcome measure is the rate of shunt failure at a 2-year follow-up term. The secondary outcomes include Keifer’s Hydrocephalus Scale, National Institute of Health Stroke Scale, Glasgow Outcome Scale Extended, Evans index, safety endpoints and cost-effectiveness of hospital stay.Ethics and disseminationThe study will be performed in compliance with the Declaration of Helsinki (2002) of the World Medical Association. The study was approved by Institutional Review Board of West China Hospital. All patients will be fully informed the potential benefits, potential risks and responsibilities, those who will sign the informed consents once they are included. Preliminary and final results will be published in peer-reviewed journals and presented at national and international congresses.Trial registration numberChiCTR2100043839.

Blood blister aneurysms (BBAs) are intracranial arterial lesions appearing in nonbranching sites of the supraclinoid internal carotid artery as well as the basilar artery. Endovascular treatment of BBAs is still not well established because of the rarity of these lesions. We report incidences of BBAs with associated vasospasms. Treatment of the BBAs and associate vasospasms with single Pipeline Flex embolization device (PLED) assisted coiling resulted in seemly shorting of the PLEDs in 3 patients. A retrospective analysis of patients with BBAs who were treated with single PLED assisted coiling from July 2018 to October 2019 was conducted. Patients’ ethnic and medical records, aneurysmal characteristics, intraoperative-rupture, cerebral vasospasm (CVS), postprocedure contrast filling, follow-up imaging, and results were analyzed. Neurological examination at baseline and outcome based on modified Rankin scale (mRS) at discharge as well as follow-ups were also documented. Six patients consisting of 5 females and 1 male, with a mean age of 48.3 years (range from 34–67) were identified during our analysis. All the BBAs were located in nonbranching site of supra-clinoidal segment of internal carotid artery with a mean neck width of 4.5 mm and mean aneurysm size of 4.23 mm. PLED assisted coiling's were performed in all of them. CVS was observed in 3 patients while 1 patient had an intraoperative-rupture of the BBA. Postprocedure contrast filling was still present in 1 patient. All the patients had good outcomes with discharge and follow-up mRS scores ≤ 2 except 1 patient with mRS score = 3 with aphasia. PLED assisted endovascular coiling is very safe and efficient in treating patients with BBAs. Resolution of CVSs after treatment made the PLEDs seemly shorter. Furthermore, a combination of arterial lengthening after gaining their tensile strength back and radical expansion of the PLED could account for the shortening.

BACKGROUND: This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low‐ and middle‐income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self‐poisoning. Standard treatment for paraquat poisoning prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat‐induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination has been developed and studied as an intervention for paraquat poisoning. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide for moderate to severe oral paraquat poisoning. SEARCH METHODS: The most recent searches were run in September 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Injuries Trials Register), Ovid MEDLINE(R), Ovid MEDLINE In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, Embase Classic + Embase (Ovid), ISI WOS (SCI‐EXPANDED, SSCI, CPCI‐S, and CPSI‐SSH), and trials registries. We also searched the following three resources: China National Knowledge Infrastructure database (CNKI 数据库); Wanfang Data (万方数据库); and VIP (维普数据库) on 12 November 2020. We examined the reference lists of included studies and review papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs). For this update, in accordance with Cochrane Injuries' Group policy (2015), we included only prospectively registered RCTs for trials published after 2010. We included trials which assessed the effects of glucocorticoid with cyclophosphamide delivered in combination. Eligible comparators were standard care (with or without a placebo), or any other therapy in addition to standard care. Outcomes of interest included mortality and infections. DATA COLLECTION AND ANALYSIS: We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Where possible, we summarised data for all‐cause mortality at relevant time periods (from hospital discharge to three months after discharge) in meta‐analysis, using a fixed‐effect model. We conducted sensitivity analyses based on factors including whether participants were assessed at baseline for plasma paraquat levels. We also reported data on infections within one week after initiation of treatment. MAIN RESULTS: We included four trials with a total of 463 participants. The included studies were conducted in Taiwan (Republic of China), Iran, and Sri Lanka. Most participants were male. The mean age of participants was 28 years. We judged two of the four included studies, including the largest and most recently conducted study (n = 299), to be at low risk of bias for key domains including sequence generation. We assessed one study to be at high risk of selection bias and another at unclear risk, since allocation concealment was either not mentioned in the trial report or explicitly not undertaken. We assessed three of the four studies to be at unclear risk of selective reporting, as no protocols could be identified. An important source of heterogeneity amongst the included studies was the method of assessment of participants' baseline severity using analysis of plasma levels (two studies employed this method, whilst the other two did not). No studies assessed the outcome of mortality at 30 days following ingestion of paraquat. Low‐certainty evidence from two studies indicates that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce the risk of death in hospital compared to standard care alone ((RR 0.82, 95% CI 0.68 to 0.99; participants = 322); results come from sensitivity analysis excluding studies not assessing plasma at baseline). However, we have limited confidence in this finding as heterogeneity was high (I(2) = 77%) and studies varied in terms of size and comparators. A single large study provided data showing that there may be little or no effect of treatment at three months post discharge from hospital (RR 0.98, 95% CI 0.85 to 1.13; 1 study, 293 participants; low‐certainty evidence); however, analysis of long‐term results amongst participants whose injuries arose from self‐poisoning must be interpreted with caution. We remain uncertain of the effect of glucocorticoids with cyclophosphamide on infection within one week after initiation of the treatment; this outcome was assessed by two small studies only (31 participants, very low‐certainty evidence) that considered leukopenia as a proxy or risk factor for infection. Neither study reported infections in any participants. AUTHORS' CONCLUSIONS: Low‐certainly evidence suggests that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce mortality in hospitalised people with oral paraquat poisoning. However, we have limited confidence in this finding because of substantial heterogeneity and concerns about imprecision. Glucocorticoids with cyclophosphamide in addition to standard care may have little or no effect on mortality at three months after hospital discharge. We are uncertain whether glucocorticoid with cyclophosphamide puts patients at an increased risk of infection due to the limited evidence available for this outcome. Future research should be prospectively registered and CONSORT‐compliant. Investigators should attempt to ensure an adequate sample size, screen participants for inclusion rigorously, and seek long‐term follow‐up of participants. Investigators may wish to research the effects of glucocorticoid in combination with other treatments.

Objectives Autoimmune diseases are a heterogeneous group of diseases which lose the immunological tolerance to self‐antigens. It is well recognized that irregularly provoked T cells participate in the pathological immune responses. As a novel nanomaterial with promising applications, tetrahedral framework nucleic acid (TFNA) nanostructure was found to have immune regulatory effects on T cells in this study. Materials and Methods To verify the successful fabrication of TFNA, the morphology of TFNA was observed by atomic force microscopy (AFM) and dynamic light scattering. The regulatory effect of TFNA was evaluated by flow cytometry after cocultured with CD3+ T cells isolated from healthy donors. Moreover, the associated signaling pathways were investigated. Finally, we verified our results on the T cells from patients with neuromyelitis optica spectrum disorder (NMOSD), which is a typical autoimmune disease induced by T cells. Results We revealed the alternative regulatory functions of TFNA in human primary T cells with steady status via the JNK signaling pathway. Moreover, by inhibiting both JNK and ERK phosphorylation, TFNA exhibited significant suppressive effects on IFNγ secretion from provoking T cells without affecting TNF secretion. Similar immune regulatory effects of TFNA were also observed in autoreactive T cells from patients with NMOSD. Conclusions Overall, our results revealed a potential application of TFNA in regulating the adaptive immune system, as well as shed a light on the treatment of T cell–mediated autoimmune diseases., Tetrahedral framework nucleic acid, as a novel nanomaterial, was used in human primary T cells for the first time. TFNA could regulate the immune response of T cells compared with immunosuppressors both in physiological and pathological circumstances via the MAPK signaling pathway. TFNA could regulate the immune response of T cells in peripheral blood of patients with NMOSD ex vivo.

Glioblastoma (GBM) is one of the deadliest primary brain malignant tumors with a bleak prognosis. Craniotomy surgical resection followed by radiotherapy and chemotherapy was still the standard therapeutic strategy for GBM. As a target alkylating agent, temozolomide (TMZ) was utilized in the therapy of GBM for decades. However, effective treatment for GBM is stymied by rapid acquired resistance and bone marrow suppression. Here, we synthesize a tetrahedral framework nucleic acid (tFNA) nanoparticle that can carry TMZ to enhance the lethality on four GBM cell lines via activating the cell apoptosis and autophagy pathway. Our nanoparticle, namely, tFNA-TMZ, shows a more obvious efficacy in killing TMZ-sensitive cells (A172 and U87) than single-agent TMZ. Besides, tFNA-TMZ was able to attenuate drug resistance in TMZ-resistant cells (T98G and LN-18) via downregulating the expression of O6-methylguanine-DNA-methyltransferase. Furthermore, we modified the tFNA with GS24, a DNA aptamer that can specially bind to transferrin receptor in the cerebral vascular endothelial cell of mouse and enable the tFNA nanoparticle to cross the blood-brain barrier. In summary, our results demonstrated that tFNA-TMZ has a promising role as a nanoscale vehicle to deliver TMZ to enhance the efficacy of GBM.

To investigate whether digital breast tomosynthesis (DBT) and subsequently generated synthesized mammography (SM) images show a better performance than full-field digital mammography (FFDM) images for diagnosing malignant breast lesions. In addition, the radiation doses for SM using different procedures were compared. This prospective study enrolled 212 women (age ≥ 25 years) with clinically suspicious breast lesions. All participants underwent FFDM and DBT with the same breast compression. Finally, 222 lesions were confirmed by pathological analysis. The mammogram results were evaluated according to the BI-RADS criteria and compared with the pathological results. The diagnostic performances, morphological features and average glandular doses (AGDs) were compared. In total, 141 malignant lesions and 81 benign lesions were confirmed by pathological analysis. The overall AGD showed no significant difference between FFDM and DBT. Compared with 2D imaging, the AUC values of FFDM plus DBT and SM plus DBT were both significantly different overall (P = 0.0002) and remained significantly different in dense breasts (P

We investigated the outcomes of patients with an unruptured intracranial aneurysm (UIA) and2 risk factors concerning complications, obliteration rate, and other factors after surgical or endovascular treatment.Coiling and clipping were compared in patients with UIAs treated in West China Hospital from January 2015 to May 2017. Patient survival, dependency, retreatment, complications, and other clinical outcome indexes were compared between the 2 groups.A total of 82 patients (92 aneurysms) had undergone treatment for UIAs with multiple risk factors. Of these 82 patients, 45 (54.9%) had undergone clipping and 37 (45.1%) had undergone coiling. No deaths were related to either treatment. Morbidity (modified Rankin scale score2) at 1 year had developed in 1 of 45 and 1 of 37 patients in the clipping and coiling groups, without a statistically significant difference. Hospitalization5 days (30 of 45 vs. 12 of 37; P0.05) was less frequent after coiling. The number of aneurysms with complete occlusion (48 of 51 vs. 33 of 41; P0.05) was greater in the surgical group. No differences in peritreatment complications were found in the surgical and endovascular groups (8 of 45 vs. 6 of 37; P0.05).In our study, clipping and coiling showed advantages for the treatment of UIAs with multiple risk factors. Surgical clipping of UIAs is achievable with a low rate of unfavorable outcomes and a high rate of complete obliteration for patients with multiple risk factors. However, endovascular treatment was also successful, with a shorter length of stay and low procedure-related morbidity. Additional randomized evidence are required to support the superior efficacy of clipping.

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.

Primary intraventricular hemorrhage (PIVH) is a rare condition in adult patients. PIVH occurs frequently in adult hemorrhagic Moyamoya disease (MMD). Idiopathic PIVH is defined as PIVH without cerebrovascular abnormalities. This study is aimed to compare the baseline characteristics and outcomes of acute MMD-related and idiopathic PIVH.Adult patients with acute MMD-related or idiopathic PIVH were retrospectively included. Baseline characteristics and outcomes at discharge were obtained and compared. Chi-square test, Student's t-test, or rank-sum test were used in statistical analyses.This study finally included 32 patients with acute MMD-related PIVH and 112 with acute idiopathic PIVH. Patients with acute MMD-related PIVH were significantly younger (53.3 ± 15.8 vs. 42.8 ± 12.2 years, P0.001). The admission systolic blood pressure in patients with acute idiopathic PIVH was significantly higher (161.7 ± 30.9 vs. 134.6 ± 24.6 mm Hg, P0.001). Patients with acute idiopathic PIVH had significantly higher admission serum urea (5.68 ± 2.66 vs. 4.34 ± 1.62 mmol/L, P = 0.008), cystatin C (0.97 ± 0.72 vs. 0.68 ± 0.16 mg/L, P = 0.023), and uric acid (309.01 ± 105.97 vs. 242.24 ± 77.65 μmol/L, P = 0.001). In patients with acute MMD-related PIVH, only one (3.1%) patient was dead at discharge. In contrast, a total of 22 (19.6%) patients with acute idiopathic patients died at discharge (P = 0.027).Compared with patients with acute idiopathic PIVH, patients with acute MMD-related PIVH have younger age, lower blood pressure, and better renal function. Moreover, patients with acute MMD-related PIVH have lower short-term mortality.

With over 2 million new cases annually, stroke is associated with the highest disability-adjusted life-years lost of any disease in China. The burden is expected to increase further as a result of population ageing, an ongoing high prevalence of risk factors (eg, hypertension), and inadequate management. Despite improved access to overall health services, the availability of specialist stroke care is variable across the country, and especially uneven in rural areas. In-hospital outcomes have improved because of a greater availability of reperfusion therapies and supportive care, but adherence to secondary prevention strategies and long-term care are inadequate. Thrombolysis and stroke units are accepted as standards of care across the world, including in China, but bleeding-risk concerns and organisational challenges hamper widespread adoption of this care in China. Despite little supporting evidence, Chinese herbal products and neuroprotective drugs are widely used, and the increased availability of neuroimaging techniques also results in overdiagnosis and overtreatment of so-called silent stroke. Future efforts should focus on providing more balanced availability of specialised stroke services across the country, enhancing evidence-based practice, and encouraging greater translational research to improve outcome of patients with stroke.