Hematocrit Predicts Poor Prognosis in Patients with Acute Ischemic Stroke or Transient Ischemic Attack.

This study aims to investigate the association between HCT (Hematocrit) levels and adverse outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA); 14,832 participants from the China National Stroke Registry-III with AIS or TIA were analyzed. Participants were categorized into quartiles based on baseline HCT levels. The primary outcome was poor functional outcomes (modified Rankin Scale ≥ 3) during three months, with secondary outcomes including all-cause death, stroke recurrence, and combined vascular events. Logistic regression or Cox regression models were used to assess the relationship between HCT and clinical outcomes. Compared to the third quartile, patients in the lowest quartile group showed increased risk of poor functional outcome (adjusted OR: 1.35, 95% CI: 1.15-1.58, p < 0.001), patients in the lowest quartile had a higher risk of all-cause death (adjusted HR: 1.68, 95% CI: 1.06-2.68, p = 0.028), as did those in the highest quartile (adjusted HR: 2.02, 95% CI: 1.26-3.25, p = 0.004). Sensitivity analysis shows that the association of HCT with all-cause death weakened, while the association with poor functional outcome was strengthened after excluding patients with recurrent stroke. Our results indicated that HCT level could be used as a short-term predictor for poor functional outcomes and all-cause death in patients with AIS or TIA.

Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies. METHODS: We prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2-6] at 3 months. RESULTS: Of the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0-69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00-5.98, p = 0.049, pinteraction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12-0.76, p = 0.01, pinteraction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02-0.42, p = 0.002; pinteraction = 0.001). CONCLUSION: CHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients.

Primary Angiitis of the Central Nervous System in Adults: A Comprehensive Review of 76 Biopsy-Proven Case Reports.

Purpose: Primary angiitis of the adult central nervous system (PACNS) is an increasingly recognized but limited disease. Using previous case reports, we sought to summarize the clinical symptoms, imaging manifestations, treatment, and prognosis of patients with biopsy-confirmed PACNS to guide clinical diagnosis and management. Methods: We searched the Web of Science database for studies published from January 2000 to April 2023, with the language set to English and the document type limited to [Article or Review or Letter or Editorial Material]. A systematic review of all case reports met the inclusion and exclusion criteria was performed. These patients' clinical, pathological, and imaging characteristics were analyzed, and treatment and prognostic data were summarized. Results: We analyzed 69 articles, including 76 patients with biopsy-confirmed PACNS. And 57.9% of the patients were male, the median age at presentation was 47.0 years, and focal neurological deficits were the most common symptom in patients (78.9%), followed by headache (52.6%). The median duration of biopsy was 1.1 months, of which 49 (64.5%) patients were lymphocytic, 13 (17.1%) were granulomatous, 11 (14.5%) were amyloidotic, and 3 (3.9%) were necrotizing PACNS. Relapse events occurred in 41 (53.9%) patients, including 34 (44.2%) relapses and 8 (10.5%) deaths. Univariate logistic regression analysis revealed that symptomatic epilepsy, prolonged biopsy time window, and CD20 expression in pathological tissues might be independent risk factors for recurrent events in patients (HR=4.69, 95% CI: 1.51-14.54, p=0.007; HR=1.11, 95% CI: 1.00-1.22, p=0.043; HR=5.33, 95% CI: 1.07-26.61, p=0.041). Conclusion: Adult PACNS is associated with frequent relapses and high mortality. Symptomatic epilepsy, prolonged biopsy time window, and CD20 expression in pathological tissue may be associated with recurrent events.

Prominent veins sign is associated with malignant cerebral edema after acute ischemic stroke.

Malignant cerebral edema (MCE) is often associated with severe physical disability and a high mortality rate. The current prediction of MCE is focused on infarct volume, and tools are relatively lacking. The prominent veins sign (PVS-SWI) is considered a marker of severely impaired tissue perfusion. This study aimed to determine whether PVS-SWI is associated with early-onset MCE. Patients with acute ischemic stroke (AIS) due to severe large arterial stenosis or occlusion (SLASO) from June 2018 to June 2020 were included. The ASPECTS score assessed the extent of PVS-SWI, and 4-10 was defined as a positive group. The primary outcome was MCE, defined as the deterioration of neurological function and midline structural excursions of >5 mm during hospitalization. The secondary outcomes included worsening of the NIHSS by ≥ 2 points, in-hospital death, and death within 1 year after stroke. Logistic regression was used to assess the correlation between PVS-SWI and outcomes. The study included 157 patients， 40 (25.5%) of whom developed MCE. PVS-SWI was more prevalent in patients who developed MCE (75.0% vs 45.3%; P = 0.001). In multivariate regression analysis, PVS-SWI was an independent predictor of MCE development in patients with larger infarct sizes (OR: 4.00， 95%CI: 1.54-10.35，p = 0.004). In patients with small infarct sizes, PVS-SWI was an independent predictor of a worsening NIHSS of ≥2(OR: 11.13， 95%CI: 2.26-54.89， p = 0.003）. However, PVS-SWI was not associated with death. The main finding of our study was that in patients with larger infarct sizes, a positive PVS-SWI increased the risk of developing MCE. In these patients, more interventions may be needed.

Stroke risk after varicella-zoster virus infection: a systematic review and meta-analysis.

Varicella-zoster virus (VZV) infection may cause vascular inflammatory changes leading to an increased risk of stroke. Previous studies have focused on the risk of stroke and less on changes in stroke risk and prognosis. We aimed to explore the changing patterns of stroke risk and stroke prognosis after VZV infection. This study is a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library for studies on stroke after VZV infection between January 1, 2000, and October 5, 2022. Relative risks were combined for the same study subgroups using a fixed-effects model and pooled across studies using a random-effects model. 27 studies met the requirements, including 17 herpes zoster (HZ) studies and ten chickenpox studies. There was an increased risk of stroke after HZ, and this risk decreased over time: relative risk 1.80 (95% CI 1.42-2.29) within 14 days, 1.61 (95% CI 1.43-1.81) within 30 days, 1.45 (95% CI 1.33-1.58) within 90 days, 1.32 (95% CI 1.25-1.39) within 180 days, 1.27 (95% CI 1.15-1.40) at one year and 1.19 (95% CI 0.90-1.59) after one year, with the same trend in the stroke subtype. The risk of stroke after herpes zoster ophthalmicus was higher, with a maximum relative risk of 2.26 (95% CI 1.35-3.78). The risk of stroke after HZ was higher in patients aged around 40 years: relative risk 2.53 (95% CI 1.59-4.02), and similar in men and women. Also, after pooling studies of post-chickenpox stroke, we found that the middle cerebral artery and its branches were most frequently involved (78.2%), with a better prognosis in most patients (83.1%) and less frequent vascular persistence progression (8.9%). In conclusion, the risk of stroke increases after VZV infection, decreasing over time. Post-infection vascular inflammatory changes often occur in the middle cerebral artery and its branches, with a better prognosis in most patients and less frequent persistent progression.

A coumarin-based fluorescent probe: single-wavelength excitation, discrimination of Cys/Hcy and GSH by naked eyes.

Biothiols mainly include cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), which play an important role in life activities and abnormal changes in their concentrations are closely related to certain diseases. Therefore, the quantitative tracking and analysis of biothiols in living organisms has become a hot research topic in recent years. In this work, a coumarin-based fluorescent probe COUN was designed and synthesized for the comparable color recognition of Cys/Hcy and GSH by introducing the phenylethynyl group as the recognition site of biothiols, which showed significant fluorescence enhancement and green fluorescence under the UV light at 365 nm. The probe specifically recognized Hcy, showing 40-fold fluorescence enhancement and strong green fluorescence at 492 nm. Moreover, there was a good linear relationship between the fluorescence intensity of the probe and certain concentrations of Cys/Hcy and GSH, with detection limits of 36.6 nM, 86.4 nM, and 174 nM, respectively. The recognition mechanism of COUN to distinguish Cys/Hcy and GSH was studied by TDDFT calculations. More importantly, COUN was successfully used for imaging biothiols in living cells. The results showed that this probe could provide an effective contribution to the understanding of the role of biothiols, especially Hcy.

Association of sex and age with in-hospital mortality and complications of patients with intracerebral hemorrhage: A study from the Chinese Stroke Center Alliance.

BACKGROUND AND PURPOSE: The impact of sex and age on prognosis in patients with intracerebral hemorrhage (ICH) in the Chinese population remains unclear. Our study aimed to investigate the relationship between sex and age of Chinese ICH patients and adverse prognosis. METHODS: We used the Chinese Stroke Center Alliance database with in-hospital mortality as the primary outcome and hospital complications as the secondary outcome. Patients were divided into four groups by sex and age. Logistic regression analyses were performed to assess the association between sex and age and the prognosis of ICH patients. RESULTS: We enrolled 60,911 ICH patients, including 22,284 young and middle-aged males, 15,651 older males, 11,948 young and middle-aged females, and 11,028 older females. After adjusting for variables, older male patients had a higher mortality rate (OR = 1.21, 95% CI 1.01-1.45), combined with more frequent hematoma expansion (OR = 1.14, 95% CI 1.03-1.26), pneumonia (OR = 1.91, 95% CI 1.81-2.03), and hydrocephalus (OR = 1.28, 95% CI 1.04-1.59). Young and middle-aged female patients had a lower mortality rate (OR = 0.74, 95% CI 0.58-0.95) and less frequent combined pneumonia (OR = 0.81, 95% CI 0.75-0.87). In-hospital mortality was not significantly different in older females compared with young and middle-aged males, but the odds of deep vein thrombosis, swallowing disorders, urinary tract infections, and gastrointestinal bleeding were significantly higher. CONCLUSION: Among young and middle-aged patients, females are related to a lower in-hospital mortality rate from ICH. Older patients are at an increased risk of ICH complications, with higher in-hospital mortality in older men.

Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study.

BACKGROUND: Somatic mutation contributes to clonal haematopoiesis of indeterminate potential (CHIP) is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease. Here, we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke (AIS) cohort and explored the underlying mechanisms. METHODS: We studied a prospective cohort of 6016 patients who had a first-ever AIS in China. Whole-genome sequencing was performed to identify CHIP. High-sensitivity C reactive protein (hs-CRP) levels above 3 mg/L at baseline were defined as hyperinflammation. Recurrent stroke during the 3-month follow-up was the primary outcome. RESULTS: Among the 6016 patients who had a first-ever AIS, with a median age was 62 years (IQR, 54.0‒70.0), 3.70% were identified as CHIP carriers. The most common mutations occurred in the DNMT3A (30.0%) and TET2 (11.4%) genes. During a follow-up of 3 months, the presence of CHIP was associated with recurrent stroke (HR 1.62, 95% CI 1.04 to 2.51, p=0.03), recurrent ischaemic stroke (HR 1.64, 95% CI 1.04 to 2.58, p=0.03) and combined vascular events (HR 1.58, 95% CI 1.02 to 2.44, p=0.04) after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS. Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation (OR 3.10, 95% CI 1.92 to 5.00, p<0.001) but not in those without hyperinflammation (OR 0.18, 95% CI 0.03 to 1.04, p=0.06, Pinteraction=0.002). CONCLUSION: Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS. Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.

Relationship Among Homocysteine, Inflammation and Cognitive Impairment in Patients with Acute Ischemic Stroke and Transient Ischemic Attack.

PURPOSE: To investigate the associations among homocysteine (Hcy), inflammation and cognitive impairment in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA). PATIENTS AND METHODS: Patients included were enrolled from a subgroup of China National Stroke Registry-III (CNSR-III). We used a Chinese version of Montreal Cognitive Assessment (MoCA) to screen for cognitive impairment. We used high-sensitivity C-reactive protein (hsCRP) level to reflect the inflammatory status, which was assessed at baseline together with Hcy concentration. The primary outcome was the incidence of post-stroke cognitive impairment (PSCI) at 3 months after AIS and TIA. Multivariable logistic regression analysis was used to evaluate the correlation between Hcy and hsCRP, and their effects on cognition. RESULTS: We enrolled 1466 patients with a median age of 62 (54-70) years old, including 895 (61.05%) patients with elevated Hcy levels, 466 (31.79%) with increased hsCRP concentrations, and 755 (51.50%) with PSCI. In the group of patients with hyperhomocysteinemia (HHcy), higher hsCRP levels were related to cognitive impairment, whether or not adjusted for multiple potential confounders (crude OR: 1.71,95% CI: 1.29-2.27, p < 0.01; adjusted OR: 1.42, 95% CI: 1.04-1.93, p = 0.03). No significant interactions for the impact on PSCI were observed in subgroups stratified by age, sex or Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification (P interaction > 0.05 for all). CONCLUSION: High inflammatory levels increase the risk of cognitive impairment in HHcy patients after AIS and TIA.

The Prognostic Impact of Susceptibility-Weighted Imaging Prominent Veins in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

PURPOSE: We aimed to determine the prognostic impact of prominent veins (PVS) after an acute ischemic stroke identified on susceptibility-weighted imaging (PVS-SWI). METHODS: We searched for studies published in PubMed, Embase, Cochrane Library and Chinese Biomedical Literature Database. Poor functional prognosis, early neurological deterioration, and hemorrhagic transformation were evaluated. Risk ratios (RR) were pooled implementing a random effect model. We performed a subgroup analysis by treatment, location (cortical/medullary) and a sensitivity analysis by follow-up time. RESULTS: Sixteen studies were included (a total of 1605 patients) in the quantitative meta-analysis. PVS-SWI were related with a poor functional outcome (RR 1.62, 95% CI 1.25 to 2.10), especially in the patients receiving thrombolysis (RR 2.19, 95% CI 1.53 to 3.15) and an augmented risk of early neurological damage (RR 2.85, 95% CI 2.31 to 3.51). Both cortical and medullary prominent veins were accompanied by a poor functional outcome (RR 1.82, 95% CI 1.30 to 2.56/RR 2.59, 95% CI 1.98 to 3.38). PVS-SWI were not associated with poor functional outcomes when patients were treated conservatively (RR 1.35, 95% CI 0.82 to 2.22), or with an increased risk of hemorrhagic transformation (RR 0.97, 95% CI 0.64 to 1.47). CONCLUSION: PVS-SWI were related to a poor functional prognosis and an increased risk of early neurological damage. In patients treated conservatively, PVS-SWI were not accompanied by a poor prognosis. PVS-SWI were not associated with an augmented risk of hemorrhagic transformation.

Relationship Between Glycosylated Hemoglobin and Short-Term Mortality of Spontaneous Intracerebral Hemorrhage.

Background: The relationship between glycosylated hemoglobin (HbA1c) and prognosis of spontaneous intracerebral hemorrhage (SICH) patients has not been fully elucidated. This study aimed to reveal the relationship between HbA1c levels and short-term mortality after patient admission with SICH. Methods: It was a large-scale, multicenter, cross-sectional study. From August 1, 2015, to July 31, 2019, a total of 41910 SICH patients were included in the study from the Chinese Stroke Center Alliance (CSCA) program. Finally, we comprehensively analyzed the data from 21,116 patients with SICH. HbA1c was categorized into four groups by quartile. Univariate and multivariate logistic regression analyses were used to assess the association between HbA1c levels and short-term mortality in SICH patients. Results: The average age of the 21,116 patients was 62.8 ± 13.2 years; 13,052 (61.8%) of them were male, and 507 (2.4%) of them died. Compared to the higher three quartiles of HbA1c, the lowest quartile (≤5.10%) had higher short-term mortality. In subgroup analysis with or without diabetes mellitus (DM) patients, the mortality of the Q3 group at 5.60-6.10% was significantly lower than that of the Q1 group at ≤5.10%. After adjustment for potential influencing factors, the ROC curve of HbA1c can better predict the short-term mortality of patients with SICH (AUC = 0.6286 P < 0.001). Conclusions: Therefore, we concluded that low or extremely low HbA1c levels (≤5.10%) after stroke were associated with higher short-term mortality in SICH patients, with or without DM.

Regulating morphologies and near-infrared photothermal conversion of perylene bisimide via sequence-dependent peptide self-assembly.

The assembly behavior of perylene bisimide (PBI) can be precisely organised by the conjugation of sequence-dependent di-peptides in aqueous media. The assembled nanostructures and consequent properties of PBI aggregates can be tuned by the use of different peptide sequences with improved yield of radical anions and enhanced photothermal conversion efficiency.

Tuning Supramolecular Structure and Functions of Peptide bola-Amphiphile by Solvent Evaporation-Dissolution.

Solvent molecules significantly affect the supramolecular self-assembly, for example, in forming solvent-bridged hydrogen bonding networks. Even small changes in solvent composition can have dramatic impact on supramolecular assembly. Herein, we demonstrate the use of trace solvents (as low as 0.04%) to tune the morphology and consequent functions of supramolecular nanostructures based on an aromatic peptide bola-amphiphile. Specifically, perylene bisimide-(di)glycine-tyrosine (PBI-[GY]2) bola-amphiphile was shown to give rise to red-emitting nanofibers when assembled in water, while exposure to trace organic solvents such as tetrahydrofuran (THF) and others via solvent-evaporation followed by aqueous assembly gave rise to white-light-emitting nanospheres. Differential hydrogen bonding between water (donor and acceptor) and THF (acceptor only) impacts supramolecular organization, which was verified using a density functional theory (DFT) simulation. The tunable consequent surface hydrophobicity was utilized in staining the cytoplasm and membrane of cells, respectively. The trace-solvent effect achieved through evaporation-dissolution provides a methodology to mediate the morphologies and consequent functions for supramolecular biomaterials controlled by the self-assembly pathway.

Antibacterial nano-structured titania coating incorporated with silver nanoparticles.

Titanium (Ti) implants are widely used clinically but post-operation infection remains one of the most common and serious complications. A surface boasting long-term antibacterial ability is highly desirable in order to prevent implant associated infection. In this study, titania nanotubes (TiO(2)-NTs) incorporated with silver (Ag) nanoparticles are fabricated on Ti implants to achieve this purpose. The Ag nanoparticles adhere tightly to the wall of the TiO(2)-NTs prepared by immersion in a silver nitrate solution followed by ultraviolet light radiation. The amount of Ag introduced to the NTs can be varied by changing processing parameters such as the AgNO(3) concentration and immersion time. The TiO(2)-NTs loaded with Ag nanoparticles (NT-Ag) can kill all the planktonic bacteria in the suspension during the first several days, and the ability of the NT-Ag to prevent bacterial adhesion is maintained without obvious decline for 30 days, which are normally long enough to prevent post-operation infection in the early and intermediate stages and perhaps even late infection around the implant. Although the NT-Ag structure shows some cytotoxicity, it can be reduced by controlling the Ag release rate. The NT-Ag materials are also expected to possess satisfactory osteoconductivity in addition to the good biological performance expected of TiO(2)-NTs. This controllable NT-Ag structure which provides relatively long-term antibacterial ability and good tissue integration has promising applications in orthopedics, dentistry, and other biomedical devices.