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BACKGROUND: The molecular subtype of breast cancer is one of the most important factors affecting patient prognosis. The study aimed to analyze the association between quantitative and qualitative features of contrast-enhanced mammography (CEM) images and breast cancer molecular subtypes. METHODS: This retrospective double-center study included women who underwent CEM between November 2017 and April 2020. Each patient had at least 1 malignant lesion confirmed by pathology. The CEM images were evaluated by 2 radiologists to obtain quantitative and qualitative image features. The molecular subtypes were studied as dichotomous outcomes, including luminal versus non-luminal, human epidermal growth factor receptor (HER2)-enriched versus non-HER2-enriched, and triple-negative breast cancer (TNBC) versus non-TNBC subtypes. The association between the image features and molecular subtypes was analyzed by multivariate logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs) provided. RESULTS: A total of 151 patients with 160 malignant lesions were included in the study. For quantitative features, a higher standard deviation of lesion density was associated with non-luminal (OR =0.88, 95% CI: 0.81 to 0.96, P=0.004) and HER2-enriched breast cancers (OR =1.16, 95% CI: 1.04 to 1.28, P=0.006). The relative degree of enhancement (RDE) and contrast-to-noise ratio (CNR) were not associated with molecular subtypes. However, a higher CNR/lesion size (OR =1.06, 95% CI: 1.01 to 1.12, P=0.012) was associated with luminal subtype cancers, and a higher RDE/lesion size (OR =0.94, 95% CI: 0.88 to 1.00, P=0.035) or a higher CNR/lesion size (OR =0.94, 95% CI: 0.88–1.00, P=0.038) was associated with non-TNBCs. For qualitative features, the presence of calcification was associated with HER2-enriched breast cancers (OR =2.91, 95% CI: 1.10 to 7.67, P=0.031). The presence of architectural distortion was associated with luminal cancer (OR =14.50, 95% CI: 1.91 to 110.14, P=0.010) and non-TNBC (OR =0.05, 95% CI: 0.00 to 0.43, P=0.022). Non-mass enhancement (OR =2.78, 95% CI: 1.08 to 7.14, P=0.033) was associated with HER2-enriched breast cancers. An association remained after adjustments for age, breast thickness, and breast density (all adjusted P

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.

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.

Liu Zi,1,2,* Wencheng Zhou,1,3,* Jiake Xu,1,4 Junshu Li,5 Ning Li,2 Jianguo Xu,1,4,6 Chao You,1,4,6 Chengwei Wang,1,2 Meng Tian1,4,6 1Neurosurgery Research Laboratory, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Integrated Traditional and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People’s Republic of China; 6West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengwei Wang; Meng TianNeurosurgery Research Laboratory, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of ChinaTel/Fax +86 28 85164168Email 21270526@qq.com; tianmong007@gmail.comBackground: Intracerebral hemorrhage (ICH), a devastating subtype of stroke, has a poor prognosis. However, there is no effective therapy currently available due to its complex pathological progression, in which neuroinflammation plays a pivotal role in secondary brain injury. In this work, the use of statin-loaded nanomicelles to target the neuroinflammation and improve the efficacy was studied in a mouse model of ICH.Methods: Rosuvastatin-loaded nanomicelles were prepared by a co-solvent evaporation method using polyethylene glycol-poly(ϵ-caprolactone) (PEG-PCL) copolymer as a carrier. The prepared nanomicelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and then in vitro and in vivo studies were performed.Results: TEM shows that the nanomicelles are spherical with a diameter of about 19.41 nm, and DLS shows that the size, zeta potential, and polymer dispersity index of the nanomicelles were 23.37 nm, − 19.2 mV, and 0.221, respectively. The drug loading content is 8.28%. The in vivo study showed that the nanomicelles significantly reduced neuron degeneration, inhibited the inflammatory cell infiltration, reduced the brain edema, and improved neurological deficit. Furthermore, it was observed that the nanomicelles promoted the polarization of microglia/macrophages to M2 phenotype, and also the expression of the proinflammatory cytokines, such as IL-1β and TNF-α, was significantly down-regulated, while the expression of the anti-inflammatory cytokine IL-10 was significantly up-regulated. The related mechanism was proposed and discussed.Conclusion: The nanomicelles treatment suppressed the neuroinflammation that might contribute to the promoted nerve functional recovery of the ICH mouse, making it potential to be applied in clinic.Keywords: rosuvastatin, nanomicelles, neuroinflammation, intracerebral hemorrhage

Intracerebral hemorrhage (ICH) will be accompanied by the overload of iron and reactive oxygen species (ROS) following hematoma clearance. Although deferoxamine (DFO) has been widely utilized as a clinical first-line siderophore to remove the iron overload, the ROS-inducing damage still greatly limits the therapeutic effect of DFO. To address this issue, we designed and fabricated a series of dual-functional macromolecular nanoscavengers featuring high-density DFO units and catechol moieties. Note that the former units could effectively remove the iron overload, while the latter ones could efficiently deplete the ROS. The resulting nanoscavengers efficiently down-regulate the iron and ROS levels as well as significantly reduce the cell death in both iron-overloaded RAW 264.7 cells and the ICH mice model. This work suggests a novel clue for the ICH-ameliorated iron-depleting interventional therapeutic regimen.

ObjectiveStroke is a leading cause of death and disability worldwide. Neuroprotective approaches have failed in clinical trials, thus warranting therapeutic innovations with alternative targets. The gut microbiota is an important contributor to many risk factors for stroke. However, the bidirectional interactions between stroke and gut microbiota remain largely unknown.DesignWe performed two clinical cohort studies to capture the gut dysbiosis dynamics after stroke and their relationship with stroke prognosis. Then, we used a middle cerebral artery occlusion model to explore gut dysbiosis post-stroke in mice and address the causative relationship between acute ischaemic stroke and gut dysbiosis. Finally, we tested whether aminoguanidine, superoxide dismutase and tungstate can alleviate post-stroke brain infarction by restoring gut dysbiosis.ResultsBrain ischaemia rapidly induced intestinal ischaemia and produced excessive nitrate through free radical reactions, resulting in gut dysbiosis with Enterobacteriaceae expansion. Enterobacteriaceae enrichment exacerbated brain infarction by enhancing systemic inflammation and is an independent risk factor for the primary poor outcome of patients with stroke. Administering aminoguanidine or superoxide dismutase to diminish nitrate generation or administering tungstate to inhibit nitrate respiration all resulted in suppressed Enterobacteriaceae overgrowth, reduced systemic inflammation and alleviated brain infarction. These effects were gut microbiome dependent and indicated the translational value of the brain–gut axis in stroke treatment.ConclusionsThis study reveals a reciprocal relationship between stroke and gut dysbiosis. Ischaemic stroke rapidly triggers gut microbiome dysbiosis with Enterobacteriaceae overgrowth that in turn exacerbates brain infarction.

Many blood blister aneurysms (BBAs) have been documented with a rapid progression history in repeated angiography. The underlying mechanism and clinical significance remained elusive. This current study aims to clarify the clinical and histopathological differences between short-term progressive BBA and non-progressive BBAs. Eighty-one patients with BBAs were consecutively included for this single-center retrospective analysis. Clinical and radiological data on these patients were retrieved from 2017 to 2019. BBAs were defined as either progressive or non-progressive based on observed growth based on repeated imaging. Histopathological examinations of a saccular aneurysm, a progressive BBA, and a non-progressive BBA were conducted using representative aneurysm samples. Among all enrolled patients, 26 of the them were identified with progressive BBAs, while the other 55 with non-progressive BBAs. Progressive BBAs were diagnosed significantly earlier in angiography (3.36 ± 0.61 vs. 6.53 ± 1.31 days, p < 0.05) and showed a higher presence rate of daughter sacs (61.5 vs. 38.2%, p < 0.05). Three different progression patterns were identified. BBAs that developed daughter sac enlargement are diagnosed significantly later than BBAs exhibiting other progression patterns. Patients with progressive and non-progressive BBAs exhibited similar overall clinical outcomes and incidence for complications. For patients with non-progressive BBAs, microsurgery appears to be inferior to endovascular treatment, while for patients with progressive BBAs, the short-term outcomes between microsurgery and endovascular treatment were identical. Histopathological analysis revealed that both subtypes shared a similar pseudoaneurysms structure, but non-progressive BBAs had more histologically destructed aneurysm wall with less remnant fibrillar collagen in adventitia. Progressive and non-progressive BBAs may not be distinct pathological lesions but represent different stages during the BBA development. Early intervention, regardless of treatment methods, is recommended for salvageable patients with progressive BBAs, but microsurgery should be performed with caution for non-progressive BBAs due to increased surgical risk.

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.

Lijuan Shen,1,2,* Xiaowen Ma,2,3,* Tingting Jiang,2,3 Xigang Shen,2,3 Wentao Yang,3,4 Chao You,2,3 Weijun Peng2,3 1Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 2Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijun Peng; Chao YouFudan University Shanghai Cancer Center, No. 270, Dongan Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86-15026544096; +86-21-64175590Fax +86-21-64174774Email cjr.pengweijun@vip.163.com : youchao8888@aliyun.comPurpose: To explore the potential factors influencing the malignancy risk of amorphous calcifications and establish a predictive nomogram for malignancy risk stratification.Patients and Methods: Consecutive mammograms from January 2013 to December 2018 were retrospectively reviewed. Traditional clinical features were recorded, and mammographic features were estimated according to the 5th BI-RADS. Included calcifications were randomly divided into the training and validation cohorts. A nomogram was developed to graphically predict the risk of malignancy (risk) based on stepwise multivariate logistic regression analysis. The discrimination and calibration performance of the model were assessed in both the training and validation cohorts.Results: Finally, 1018 amorphous calcifications with final pathological results in 907 women were identified with a malignancy rate of 28.4% (95% CI: 25.7%, 31.3%). The malignancy rates of subgroups divided by the distribution of calcifications, quantity of calcifications, age, menopausal status and family history of cancer were significantly different. There were 712 cases and 306 cases in the training and validation cohorts. The prediction nomogram was finally developed based on four risk factors, including age and distribution, maximum diameter and quantity of calcifications. The AUC of the nomogram was 0.799 (95% CI: 0.761, 0.836) in the training cohort and 0.795 (95% CI: 0.738, 0.852) in the validation cohort.Conclusion: On mammography, the distribution, maximum diameter and quantity of calcifications are independent predictors of malignant amorphous calcifications and can be easily obtained in the clinic. The nomogram developed in this study for individualized malignancy risk stratification of amorphous calcifications shows good discrimination performance.Keywords: breast cancer, mammography, calcifications, malignancy risk stratification, nomogram

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.

Background and Purpose As a leading cause of disability and death in China, stroke as well as its epidemiologic features have gained increasing attention. Prior studies, however, have overgeneralized the north-to-south gradient in China. Whether the differences exist across urban and rural areas remains unexplored. This study therefore aims to investigate the north-to-south gradient in stroke incidence across urban and rural China.Methods The present prospective cohort study analyzed data from the China Health and Nutrition Survey 1997 to 2015. By including 16,917 individuals from diverse social contexts, we calculated the age-standardized incidence of stroke across regions and the age-adjusted risk ratio (aRR). Cox proportional hazards models with time-varying covariates were employed to analyze variations in incident stroke.Results During the follow-up, age-standardized incidence of stroke ranged from 4.17 per 1,000 person-years (95% confidence interval [CI], 3.38 to 4.96) in the north region to 1.95 (95% CI, 1.60 to 2.30) in the south region (aRR, 2.04; 95% CI, 1.58 to 2.64; P

OBJECTIVEThe intracranial hematoma volume in patients with traumatic brain injury is a key parameter for the determination of the management approach and outcome. Apolipoprotein E (APOE) ε4 is reported to be a risk factor for larger hematoma volume, which might contribute to a poor outcome. However, whether APOE ε4 is related to progressive hemorrhagic injury (PHI), a common occurrence in the clinical setting, remains unclear. In this study, the authors aimed to investigate the association between the APOE genotype and occurrence of PHI.METHODSThis prospective study included a cohort of 123 patients with traumatic intracerebral hemorrhage who initially underwent conservative treatment. These patients were assigned to the PHI or non-PHI group according to the follow-up CT scan. A polymerase chain reaction and sequencing method were carried out to determine the APOE genotype. Multivariate logistic regression analysis was applied to identify predictors of PHI.RESULTSThe overall frequency of the alleles was as follows: E2/2, 0%; E2/3, 14.6%; E3/3, 57.8%; E2/4, 2.4%; E3/4, 22.8%; and E4/4, 2.4%. Thirty-four patients carried at least one allele of ε4. In this study 60 patients (48.8%) experienced PHI, and the distribution of the alleles was as follows: E2/2, 0%; E2/3, 5.7%; E3/3, 22.8%; E2/4, 2.4%; E3/4, 16.3%; and E4/4, 1.6%, which was significantly different from that in the non-PHI group (p = 0.008). Additionally, the late operation rate in the PHI group was significantly higher than that in the non-PHI group (24.4% vs 11.4%, p = 0.002). Multivariate logistic regression identified APOE ε4 (OR 5.14, 95% CI 2.40–11.62), an elevated international normalized ratio (OR 3.57, 95% CI 1.61–8.26), and higher glucose level (≥ 10 mmol/L) (OR 3.88, 95% CI 1.54–10.77) as independent risk factors for PHI. Moreover, APOE ε4 was not a risk factor for the coagulopathy and outcome of the patients with traumatic intracerebral hemorrhage.CONCLUSIONSThe presence of APOE ε4, an elevated international normalized ratio, and a higher glucose level (≥ 10 mmol/L) are predictors of PHI. Additionally, APOE ε4 is not associated with traumatic coagulopathy and patient outcome.

Background Intracranial aneurysm (IA) is a debilitating cerebrovascular degeneration. Current clinical diagnosis relies mainly on conventional angiogram except for some peculiar aneurysms. Nonetheless, there is no documentation of aneurysm showing robust intracranial artifact on computed tomography or magnetic resonance imaging. Case Description Herein, we report a 45-year-old female with an IA showing a robust intracranial metal artifact. During surgery, the culprit lesion for the artifact was discovered to be hard plaque on the ventral part of the aneurysm. Craniotomy clipping and vessel reconstruction were successful, but minor vasospasm was observed postoperatively. Postoperative pathology and optical emission spectrometer analyses showed elevated iron and copper level in the plaque on the IA. After comparing with other aneurysm samples, we believe the overenriched local iron deposition contributed to the metal artifact on imaging. Conclusions Taken together, accidental findings of intracranial metal artifacts on computed tomography and magnetic resonance imaging can be indicative to iron deposition on intracranial aneurysm. Neuroimaging using magnetic field should be performed with caution. Local accumulation of lysed products from erythrocyte might contribute to the occurrence of this enriched iron deposition, but further evidence regarding the pathogenesis of copper deposition should be provided. Surgically, measures should be taken to avoid perioperative complications like vasospasm and delayed cerebral ischemia. Future report of similar cases would be helpful in optimizing the treatment modality for the aneurysm with metallic plaque.

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: 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.

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 investigate whether the radiomics signature (Rad-score) of DCE-MRI images obtained in triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NAC) is associated with disease-free survival (DFS). Develop and validate an intuitive nomogram based on radiomics signatures, MRI findings, and clinicopathological variables to predict DFS.Methods: Patients (n = 150) from two hospitals who received NAC from August 2011 to May 2017 were diagnosed with TNBC by pathological biopsy, and follow-up through May 2020 was retrospectively analysed. Patients from one hospital (n = 109) were used as the training group, and patients from the other hospital (n = 41) were used as the validation group. ROIs were drawn on 1.5 T MRI T1W enhancement images of the whole volume of the tumour obtained with a 3D slicer. Radiomics signatures predicting DFS were identified, optimal cut-off value for Rad-score was determined, and the associations between DFS and radiomics signatures, MRI findings, and clinicopathological variables were analysed. A nomogram was developed and validated for individualized DFS estimation.Results: The median follow-up time was 53.5 months, and 45 of 150 (30.0%) patients experienced recurrence and metastasis. The optimum cut-off value of the Rad-score was 0.2528, which stratified patients into high- and low-risk groups for DFS in the training group (pConclusion: The Rad-score derived from preoperative MRI features is an independent biomarker for DFS prediction in patients with TNBC to NAC, and the combined radiomics nomogram improved individualized DFS estimation.

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.

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.

ObjectivesTo evaluate the association of breast cancer with both the background parenchymal enhancement intensity and volume (BPEI and BPEV, respectively) and the amount of fibroglandular tissue (FGT) using an automatic quantitative assessment method in breast magnetic resonance imaging (MRI).Materials and MethodsAmong 17,274 women who underwent breast MRI, 132 normal women (control group), 132 women with benign breast lesions (benign group), and 132 women with breast cancer (cancer group) were randomly selected and matched by age and menopausal status. The area under the receiver operating characteristic curve (AUC) was compared in Cancer vs Control and Cancer vs Benign groups to assess the discriminative ability of BPEI, BPEV and FGT.ResultsCompared with the control groups, the cancer group showed a significant difference in BPEV with a maximum AUC of 0.715 and 0.684 for patients in premenopausal and postmenopausal subgroup, respectively. And the cancer group showed a significant difference in BPEV with a maximum AUC of 0.622 and 0.633 for patients in premenopausal and postmenopausal subgroup, respectively, when compared with the benign group. FGT showed no significant difference when breast cancer group was compared with normal control and benign lesion group, respectively. Compared with the control groups, BPEI showed a slight difference in the cancer group. Compared with the benign group, no significant difference was seen in cancer group.ConclusionIncreased BPEV is correlated with a high risk of breast cancer While FGT is not.

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.

Objective: Stroke is a leading cause of mortality and morbidity globally. This study aimed to analyze the burden and 30-year trends of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in China.Methods: Data that include incidence and mortality of stroke in China from January 1, 1990 to December 31, 2019 were derived from the Global Burden of Disease (GBD) study 2019. The absolute numbers of incident cases and deaths over the time, and age-standardized rates per 100,000, such as age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR), were analyzed.Results: In 2019, there were 3.9 (95% uncertainty intervals (UI) 3.4–4.5) million incident cases and 2.1 (3.4–4.5) million deaths related to stroke in China. The ASIR and ASMR of stroke in China was 200 (176–230) and 127 (110–144). From 1990 to 2019, the ASIR of ischemic stroke had increased by 35.0% (29.0–40.0) while the ASIR of ICH and SAH had decreased by −53.0% (−56.0 to −50.0) and by −39.0% (−44.0 to −35.0), respectively. The ASMR of ischemic stroke had increased by 3.0% (−26.0 to 16.0) while the ASMR of ICH and SAH had decreased by −48.0% (−59.0 to −38.0) and by −84.0% (−89.0 to −69.0), respectively.Conclusion: Although the incidence and mortality rates of stroke in China were decreased from 1990 to 2019, the number of incident cases and deaths nearly doubled. A sharp increase in the incidence rate of ischemic stroke was observed. A higher incidence rate of ischemic stroke in the women was also observed.

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: Early shunt obstruction (SO) remains the most common cause of lumboperitoneal shunt (LPS) failure. Although there is anecdotal evidence that the level of cerebrospinal fluid (CSF) parameters might affect shunt performance, its association with early LPS obstruction in adults with post-hemorrhagic hydrocephalus (PHH) is unclear.Methods: The retrospective study was performed by reviewing the adults with PHH treated by LPS from years 2014 to 2018. We included patients with CSF samples analyzed within 1 week prior to shunt insertion or at the time of shunt insertion. Baseline characteristics of each patient were collected. The primary outcomes were the incidence rate and associated factors of SO occurring within 3 months of shunt placement. The secondary outcomes included scores on the National Institute of Health Stroke Scale (NIHSS) and Evans Index at discharge.Results: A total of 76 eligible patients were analyzed, of whom 61 were obstruction-free and 15 were early SO. The overall rate of early SO was 15.6%. The RBCs count and nucleated cells count in preoperative CSF were actually higher in patients with early SO, compared to patients in the control group. Multivariate analysis identified RBC elevation (>0 × 106/L; OR: 10.629, 95% CI: 1.238–91.224, p = 0.031) as a dependent risk factor for early SO. NIHSS dramatically decreased at discharge while the alteration of ventricular size was not observed.Conclusions: This study suggested that the presence of RBCs in preoperative CSF was associated with early SO in patients with PHH treated by LPS.

Background: Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness of different classes of medication. We performed a Bayesian network meta-analysis to compare and rank the efficacy and safety of five drug regimens to determine the best treatment for this group of patients.Methods: We systematically searched PubMed, Medline, clinicaltrials.gov, the Cochrane database, and Embase to identify relevant randomized clinical trials (RCTs) comparing drug treatments in adult patients with CSDH. A network meta-analysis was conducted using a Bayesian framework. Random- and fixed-effects models were used to pool the network results, and the preferred model was selected by comparing the deviance information criteria (DIC). Efficacy outcomes included recurrence requiring surgery, changes in hematoma volume, and a good recovery. The safety outcomes were treatment-related adverse events and all-cause mortality.Results: In this Bayesian network meta-analysis, available data were obtained from 12 eligible trials, including 2,098 patients and 5 techniques. Compared to placebo, atorvastatin (RR: 0.45, 95% CrI: 0.24–0.81) and dexamethasone (RR: 0.38, 95% CrI: 0.22–0.63) were similarly effective in reducing recurrence requiring surgery by 55% and 62%, respectively. Dexamethasone (RR: 0.46, 95% CrI: 0.23–0.91) was more effective in reducing recurrence requiring surgery than goreisan. Additionally, atorvastatin reduced the hematoma volume to a greater extent than placebo (MD: −7.44, 95% CrI: −9.49 to −5.43) or goreisan (MD: −14.09, 95% CrI: −23.35 to −4.82). Moreover, tranexamic acid (MD: −12.07, 95% CrI: −21.68 to −2.29) reduced the hematoma volume to a greater extent than goreisan. No significant differences were detected between drugs and placebo with regard to a good recovery. In terms of safety, dexamethasone (RR: 1.96, 95% CrI: 1.20–3.28) increased the risk of mortality compared to placebo.Conclusion: These findings suggest that dexamethasone is the best treatment to reduce recurrence and atorvastatin is the best treatment to reduce hematoma volume in patients with CSDH. However, clinicians should pay close attention to the elevated risk of all-cause mortality and potential adverse events caused by dexamethasone. Future well-designed RCTs with more participants are needed to verify these findings.Clinical Trial Registration:http://osf.io/u9hqp.

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.

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that is associated with high morbidity and mortality. However, up to now, there are no effective prevention methods or specific therapies to improve its clinical outcomes. Herein, we explore preliminarily the efficacy of crocin, a carotenoid extracted from the stigma of saffron known for its anti-oxidation and free radical scavenging activities, in a mouse ICH model induced with collagenase infusion. Crocin or saline was administrated 6 h after ICH and then every 12 h for up to 7 days. Neurological scores were examined on days 1, 3, and 7 after ICH. Mice were sacrificed after1, 3, and 7 days of crocin treatment for examination of histology and immunohistochemistry. The results showed that oral administration of crocin attenuated the neurological deficits and reduced the myelin loss, neuron degeneration, iron deposition, reactive oxygen species (ROS) production and heme oxygenase-1 (HO-1) expression in the early stage of ICH, making it potential to be an ideal candidate for medical therapy of ICH in clinic.

Background Brainstem hemorrhage (BSH) is the most dangerous and devastating subtype of intracerebral hemorrhage and is associated with high morbidity and mortality. However, to date, no effective prevention methods or specific therapies have been available to improve its clinical outcomes. We preliminarily explored the efficacy of deferoxamine (DFO), a clinical chelator known for its iron-scavenging activities, in a rat model of BSH induced with collagenase infusion. Methods DFO or saline was administrated 6 hours after BSH induction and then every 12 hours for ≤7 days. The survival curve of the rats was created, and the neurological scores were examined on days 1, 3, and 7 after BSH. The rats were sacrificed after 1, 3, and 7 days of DFO treatment for histological examination and immunohistochemistry. Results The results showed that administration of DFO delayed erythrocytes lysis, reduced iron deposition, reduced reactive oxygen species generation, reduced heme oxygenase-1 expression, and alleviated brain injury such as neuron degeneration and myelin sheath injury. However, DFO did not improve the survival rate and neurobehavioral outcomes in this model. Conclusions Administration of DFO had limited therapeutic effects on collagenase-induced brainstem hemorrhage in rats. Some potential explanations were proposed, and more preclinical work is required to clarify the controversial curative effect of DFO in ICH.

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.

Background Hematoma enlargement happens in about 30% patients with intracerebral hemorrhage, which is reported to be closely correlated with poor prognosis. Swirl sign has been reported to have correlation with hematoma enlargement. This meta-analysis analyzed the accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage. Methods Five databases were searched for potentially eligible literature. Studies were included if they were about the predictive properties of swirl sign for hematoma enlargement in intracerebral hemorrhage. Sensitivity and specificity of swirl sign for hematoma enlargement prediction were pooled. Pooled positive and negative likelihood ratios were also calculated. Results Six studies with 2647 patients were finally included in meta-analysis. The pooled sensitivity and specificity of swirl sign were 0.45 (95%CI 0.32–0.59) and 0.79 (95%CI 0.73–0.84), respectively. The pooled positive likelihood ratio of swirl sign was 2.2 (95%CI 1.8–2.5). In contrast, the pooled negative likelihood ratio of swirl sign was 0.69 (95%CI 0.57–0.84). Conclusions This meta-analysis suggests that swirl sign has the relatively high specificity for hematoma enlargement prediction in patients with intracerebral hemorrhage.

Oligochitosan (OCHI) is known to have some specific biological activities. However, its interactions with blood components and related correlation with molecular structures remains to be clarified due to its growing use in biomedical areas. Herein, a series of OCHI were prepared by hydrogen peroxide induced degradation combined fractionation in ethanol solutions and their molecular structures were characterized by GPC, FTIR, 1H and 13C NMR, and then the interactions of the prepared OCHI with blood components, including red blood cells (hemolysis, deformability, and aggregation), coagulation system, complement (C3a, and C5a activation), and platelet (activation, and aggregation), were investigated. For red blood cells, OCHI has a quite low risk of hemolysis in a dose- and MW-dependent manner and the deformability and aggregation were observed in its high MW fraction. The coagulation tests revealed that OCHI is capable of a mild anticoagulation through blocking the intrinsic pathway and the anticoagulation corresponding MW was identified. In terms of complement, OCHI could inhibit C3a in a dose-dependent manner and activate C5a with its high MW fraction. In addition, there is no significant effect of OCHI on platelet activation and aggregation. Based on above results, the interactions related mechanism was discussed and proposed.

OBJECTIVERupture of arteriovenous malformations (AVMs) would result in high mortality and prevalence of disability in pediatric patients. Decisions regarding the treatment of AVMs need to weigh the risk of rupture over the course of their natural history against the possibility of creating a lesion during treatment. Multiple factors have been proposed to predict hemorrhagic presentation of pediatric patients with AVMs. The aim of this meta-analysis was to evaluate the predictors of hemorrhagic presentation in pediatric patients with AVMs.METHODSThe authors searched the PubMed and EMBASE databases. Studies reporting the predictors of hemorrhagic presentation in children with untreated brain AVMs were included. The predictive ability of identified predictors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs).RESULTSA higher risk of hemorrhagic presentation was found in AVMs with smaller size (< 3 cm, OR 2.97, 95% CI 1.94–4.54, p < 0.00001), deep venous drainage (OR 2.28, 95% CI 1.55–3.36, p < 0.0001), a single draining vein (OR 2.23, 95% CI 1.27–3.92, p = 0.005), a single feeder (OR 3.72, 95% CI 1.31–10.62, p = 0.01), a deep location (OR 1.82, 95% CI 1.22–2.72, p = 0.004), an infratentorial location (OR 2.25, 95% CI 1.19–4.26, p = 0.01), and diffuse morphology (OR 8.94, 95% CI 3.01–26.55, p < 0.0001). In addition, the AVMs with draining vein ectasia (OR 0.35, 95% CI 0.13–0.97, p = 0.04) and high Spetzler-Martin (SM) grade (OR 0.53, 95% CI 0.36–0.78, p = 0.001) had a lower risk of hemorrhagic presentation in pediatric patients.CONCLUSIONSSmaller AVMs, deep venous drainage, a single draining vein, a single feeder, deep/infratentorial location, diffuse morphology, and high SM grade were identified as positive predictors for hemorrhagic presentation. Particularly, patients with diffuse AVMs have a higher risk of hemorrhagic presentation than other factors and may need active treatments. However, factors such as age, sex, draining vein stenosis, and associated aneurysms were not associated with hemorrhagic presentation.

Background: Treatment of hypertensive brainstem hemorrhage (HBSH) is still controversial, especially for severe cases (GCS ≤ 8). With the improvement in neuroimaging and microsurgical techniques, severe HBSH is no longer considered inoperable. We analyzed comatose patients in whom radiology revealed severe HBSH. We further analyzed the outcome of cases we successfully operated on and compared surgical intervention with conservative management. Methods: We retrospectively analyzed data obtained from patients with HBSH who represented at our facility from 2005 to 2015. We evaluated their demographics data, lesion characteristics, surgical approaches, as well as outcomes. We further assessed their outcomes with the Glasgow Outcome Scale (GOS). We also compared the outcome of surgical hematoma evacuation with conservative treatment. Results: A total of 286 adult patients with severe HBSH was included in the study. Forty-six (46) patients were treated via craniotomy and the evacuation of the hematoma within 3 h to 2 days on admission at the emergency department. Ultra-early surgery (within 6 h of ictus) was performed in twenty (20) cases (43.5%). 240 patients were managed conservatively. The mortality rate for surgical group was 14/46 (30.4%) while the conservative group was 169/240(70.4%). The timing of surgical intervention was one of the strongest factors affecting outcome GOS (p = 0.02). The volume of the hematoma, GCS score on admission and the presence of acute hydrocephalus also affected the outcome (p = 0.03 respectively). Conclusions: Our data suggest that early surgical intervention is very crucial in achieving successful outcomes in patients with severe HBSH. Keywords: Brainstem, cerebral hemorrhage, Hypertension, Microsurgery, Neuroimaging, Outcome

Objective Among several novel predictors on noncontrast computed tomography (CT) for hematoma expansion in spontaneous intracerebral hemorrhage (sICH), shape irregularity grade, satellite sign, and island sign are all related to irregular shape of hematoma. This study is aimed to compare the accuracy of these imaging markers for predicting hematoma expansion in the same cohort of sICH patients. Methods This retrospective study enrolled sICH patients who underwent diagnostic computed tomography (CT) scans within 6 hours after onset and another follow-up CT scan within 24 hours after initial CT scan. Shape irregularity grade, satellite sign, and island sign were assessed according to the definitions in previous studies. The accuracy of these imaging indicators for predicting hematoma expansion was analyzed using receiver operator analysis. Results Finally, a total of 196 patients were included. Shape irregularity grade ≥3 was found in 87 (44.39%) patients, satellite sign was identified in 76 (38.78%) patients, and island sign was shown in only 41 (20.92%) patients. Only island sign remained an independent predictor for hematoma expansion in multivariate logistic regression. The sensitivity values of shape irregularity grade ≥3, satellite sign, and island sign were 0.52, 0.63, and 0.48, respectively. By contrast, the specificity values of these 3 predictors were 0.58, 0.69, and 0.85, respectively. Shape irregularity grade ≥3 had the smallest area under the curve (0.597), and island sign had the largest (0.676). Conclusions Island sign seems to be the optimal shape-related predictor for hematoma expansion in sICH patients and could be included in the future predictive model for hematoma expansion.

Background The island sign is a novel imaging predictor for early hematoma growth, implying multifocal active bleeding. The prognostic value of the island sign for long-term outcome in patients with intracranial hemorrhage (ICH) remains unrevealed. The aim of this study is to investigate associations between the island land and long-term prognosis in patients with ICH. Methods Both clinical characteristics and radiologic parameters were retrospectively obtained from electronic medical records. According to the initial and follow-up computed tomography scans of patients, hematoma expansion and the island sign were determined independently with 2 experienced physicians. Multivariate logistic regression analyses were used to explore the associations of hematoma expansion, 1-year poor outcome, and 1-year death on other clinical variables. Results A total of 322 patients were included, and 126 of them presented with early hematoma expansion, with 81 exhibiting the island sign. There were 116 patients who died, and 157 patients with ICH had poor outcome at the first year after onset. The multivariate logistic regression analyses revealed that initial Glasgow Coma Scale score, hematoma size, and presence of intraventricular hemorrhage and island sign were strongly associated with long-term poor outcomes. Conclusions The island sign is an easy-to-use and novel imaging marker which predicts both early hematoma expansion and long-term poor prognosis.

Background and Purpose: The systemic immune–inflammation index (SII) is a novel prognostic index in various diseases. We evaluated the predictive value of SII in patients with intracerebral hemorrhage (ICH).Methods: Patients with primary spontaneous ICH were enrolled. SII was constructed based on peripheral platelet (P), neutrophil (N), and lymphocyte (L) and defined as P*N/L. In addition to admission testing, acute phase SII was collected to analyze the potential dynamic change. Poor outcome was defined as modified Rankin Scale of more than 3 at 90 days.Results: We included 291 patients; 98 (34%) achieved favorable functional outcomes. Day-1 SII was higher and was more related to poor outcome than was admission SII. Median time of day-1 SII was 29 h from onset. Day-1 SII had an OR in outcome (mRS >3) 1.74 (95% CI = 1.03–3.00, p = 0.04). The binary cutoff point of SII calculated using the area under the curve (AUC) method was 1,700 × 109/L, AUC 0.699 (95% CI = 0.627–0.774) (sensitivity 53.3%, specificity 77.3%) (OR = 2.36, 95% CI = 1.09–5.26, p = 0.03).Conclusions: SII, especially day-1 SII, was highly associated with 90-day functional outcome in patients with ICH and could be used to predict outcomes.

Inflammation plays an important role in the pathophysiology of subarachnoid hemorrhage (SAH). Recent studies have indicated that the albumin to fibrinogen ratio (AFR) is a useful biomarker of inflammation. This research aimed to determine the ability of AFR to predict the prognosis of patients with SAH. A total of 440 patients with SAH who had been diagnosed within 72 hours of symptom onset were retrospectively reviewed. Clinical findings and laboratory data were retrieved from the hospital database. Functional outcome was measured according to the modified Rankin scale at 30 days. Logistic regression analysis was used to evaluate the correlation between AFR and the prognosis of patients with SAH. Receiver operating characteristic (ROC) analysis was performed to determine the prognostic ability of AFR at admission to predict the 30-day outcomes. The average age of all 440 patients with SAH was 56.75 ± 11.19 years and 31.4% (138) were male. Of these patients, 161 exhibited unfavorable outcomes at 30 days. According to the multivariate logistic regression analysis, the AFR was positively correlated with the outcome of patients with SAH (odds ratio 0.939, 95% confidence interval 0.885–0.996, P = .038). The ROC analysis revealed an area under the curve of 0.713 for AFR's ability to predict the 30-day outcomes. AFR is independently associated with the outcome of SAH patients. As a parameter that can be easily assessed at admission, AFR could be used to help the decision-making of clinical treatment.

Background: The optimal monoclonal antibody against calcitonin gene-related peptide (CGRP) for adult patients with migraine has yet to be determined. Therefore, we aimed to compare the effectiveness of different monoclonal antibodies against CGRP or its receptor for adult patients with migraine through a network meta-analysis of randomized controlled trials.Methods: We systematically searched the MEDILNE, Embase, ClinicalTrials.gov, and Cochrane Library databases for relevant publications from inception until October 30, 2020. Only randomized clinical trials of adults with migraine that assessed any calcitonin gene-related peptide monoclonal antibody and reported clinical outcomes were included. The primary outcomes were changes in monthly migraine days and treatment-emergent adverse eventsResults: We initially retrieved 2,070 publications, and ultimately, 18 randomized clinical trials totaling 8,926 patients were included. In terms of efficacy, eptinezumab (MD −1.43, 95% CrI −2.59 to −0.36), erenumab (MD −1.61, 95% CrI −2.40 to −0.84), fremanezumab (MD −2.19, 95% CrI −3.15 to −1.25), and galcanezumab (MD −2.10, 95% CrI −2.76 to −1.45) significantly reduced MMDs compared with placebo. In terms of safety, only galcanezumab increased the incidences of TEAEs (RR 1.11, 95% CrI 1.01–1.22) and serious adverse events (RR 2.95, 95% CrI 1.41–6.87) compared with placebo.Conclusion: Most drugs performed similarly and were superior to placebo in most of our analyses. Further head-to-head research on different types of CGRP monoclonal antibodies is necessary to validate the present findings.

Breast tumor morphological and vascular characteristics can be changed during neoadjuvant chemotherapy (NACT). The early changes in tumor heterogeneity can be quantitatively modeled by longitudinal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which is useful in predicting responses to NACT in breast cancer. In this retrospective analysis, 114 female patients with unilateral unifocal primary breast cancer who received NACT were included in a development (n = 61) dataset and a testing dataset (n = 53). DCE-MRI was performed for each patient before and after treatment (two cycles of NACT) to generate baseline and early follow-up images, respectively. Feature-level changes (delta) of the entire tumor were evaluated by calculating the relative net feature change (deltaRAD) between baseline and follow-up images. The voxel-level change inside the tumor was evaluated, which yielded a Jacobian map by registering the follow-up image to the baseline image. Clinical information and the radiomic features were fused to enhance the predictive performance. The area under the curve (AUC) values were assessed to evaluate the prediction performance. Predictive models using radiomics based on pre- and post-treatment images, Jacobian maps and deltaRAD showed AUC values of 0.568, 0.767, 0.630 and 0.726, respectively. When features from these images were fused, the predictive model generated an AUC value of 0.771. After adding the molecular subtype information in the fused model, the performance was increased to an AUC of 0.809 (sensitivity of 0.826 and specificity of 0.800), which is significantly higher than that of the baseline imaging- and Jacobian map-based predictive models (p = 0.028 and 0.019, respectively). The level of tumor heterogeneity reduction (evaluated by texture feature) is higher in the NACT responders than in the nonresponders. The results suggested that changes in DCE-MRI features that reflect a reduction in tumor heterogeneity following NACT could provide early prediction of breast tumor response. The prediction was improved when the molecular subtype information was combined into the model.

BACKGROUND: To determine the histopathological and MRI features of BRCA1/2 mutation-associated familial breast cancers compared with those of BRCA1/2 mutation-negative and sporadic breast cancers and to further compare the imaging features of cancers from BRCA1 and BRCA2 mutation carriers according to lesion type on MRI. METHODS: A retrospective review of medical records was conducted to determine tumour clinicopathologic features and MRI characteristics between June 2011 and July 2017, and 93 lesions with BRCA mutations, 93 lesions without BRCA mutations from familial breast cancers and 93 lesions from sporadic breast cancers were included. Histopathologic data, including immunohistochemistry findings and MRI data according to the BI-RADS lexicon, were reviewed. The association between MRI or histopathologic findings and BRCA mutations was analysed. RESULTS: BRCA-positive familial breast cancers had a higher number of IDCs with high nuclear grade and lymph node metastasis (all P

Digital breast tomosynthesis (DBT) is an emerging breast cancer screening and diagnostic modality that uses quasi-three-dimensional breast images to provide detailed assessments of the dense tissue within the breast. In this study, a framework of a 3D-Mask region-based convolutional neural network (3D-Mask RCNN) computer-aided diagnosis (CAD) system was developed for mass detection and segmentation with a comparative analysis of performance on patient subgroups with different clinicopathological characteristics. To this end, 364 samples of DBT data were used and separated into a training dataset (n = 201) and a testing dataset (n = 163). The detection and segmentation results were evaluated on the testing set and on subgroups of patients with different characteristics, including different age ranges, lesion sizes, histological types, lesion shapes and breast densities. The results of our 3D-Mask RCNN framework were compared with those of the 2D-Mask RCNN and Faster RCNN methods. For lesion-based mass detection, the sensitivity of 3D-Mask RCNN-based CAD was 90% with 0.8 false positives (FPs) per lesion, whereas the sensitivity of the 2D-Mask RCNN- and Faster RCNN-based CAD was 90% at 1.3 and 2.37 FPs/lesion, respectively. For breast-based mass detection, the 3D-Mask RCNN generated a sensitivity of 90% at 0.83 FPs/breast, and this framework is better than the 2D-Mask RCNN and Faster RCNN, which generated a sensitivity of 90% with 1.24 and 2.38 FPs/breast, respectively. Additionally, the 3D-Mask RCNN achieved significantly (p < 0.05) better performance than the 2D methods on subgroups of samples with characteristics of ages ranged from 40 to 49 years, malignant tumors, spiculate and irregular masses and dense breast, respectively. Lesion segmentation using the 3D-Mask RCNN achieved an average precision (AP) of 0.934 and a false negative rate (FNR) of 0.053, which are better than those achieved by the 2D methods. The results suggest that the 3D-Mask RCNN CAD framework has advantages over 2D-based mass detection on both the whole data and subgroups with different characteristics.