Predictors of early versus delayed neurological deterioration after thrombolysis for ischemic stroke: ENCHANTED study.

BACKGROUND AND PURPOSE: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND were defined as scores of a ≥2 point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥1 point decrease on Glasgow coma scale, or death, from baseline to 24 hours and 24 hours to 72 hours, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs 0-1 and 3-6 vs 0-2, and death). RESULTS: Of 4496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 hours, were all independent predictors for both END (all P ≤0.01) and DND (all P ≤0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 hours (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 hours were the key predictor of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all P<0.001). CONCLUSIONS: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for acute ischemic stroke. Both END and DND predict unfavorable outcomes at 90 days.

The prognostic value of combined uric acid and neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA is related to the prognosis of AIS patients undergoing intravenous thrombolysis (IVT) remains inconclusive. We sought to explore the combined effect of UA and NLR on the prognosis of AIS treated with IVT. METHODS: A total of 555 AIS patients receiving IVT treatment were enrolled. Patients were categorized into four groups according to the levels of UA and NLR: LNNU (low NLR and normal UA), LNHU (low NLR and high UA), HNNU (high NLR and normal UA), and HNHU (high NLR and high UA). Multivariable logistic regression analysis was used to evaluate the value of serum UA level and NLR in predicting prognosis. The primary outcomes were major disability (modified Rankin scale (mRS) score 3-5) and death within 3 months. RESULTS: After multivariate adjustment, a high NLR (≥ 3.94) increased the risk of 3-month death or major disability (OR, 2.23; 95% CI, 1.42 to 3.55, p < 0.001). However, there was no statistically significant association between a high UA level (≥ 313.00 µmol/L) and clinical outcome. HNHU was associated with a 5.09-fold increase in the risk of death (OR, 5.09; 95% CI, 1.31-19.83; P value = 0.019) and a 1.98-fold increase in the risk of major disability (OR, 1.98; 95% CI 1.07-3.68; P value = 0.030) in comparison to LNNU. CONCLUSIONS: High serum UA levels combined with high NLR were independently associated with 3-month death and major disability in AIS patients after IVT.

CT texture-based nomogram in ischaemic stroke to differentiate intracerebral hemorrhage from contrast extravasation after thrombectomy.

INTRODUCTION: Post-thrombectomy intraparenchymal hyperdense (PTIH) in patients with acute ischaemic stroke (AIS) is a common CT sign, making it difficult for physicians to distinguish intracerebral hemorrhage in the early post-thrombectomy period. The aim of this study is to develop an effective model to differentiate intracerebral hemorrhage from contrast extravasation in patients with PTIH. METHODS: We retrospectively collected information on patients who underwent endovascular thrombectomy (EVT) at two stroke centers between August 2017 and January 2023. A total of 222 patients were included in the study, including 118 patients in the development cohort, 52 patients in the internal validation cohort and 52 patients in the external validation cohort. The nomogram was constructed using R software based on independent predictors derived from the multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images. The performance and accuracy of the derived nomogram was assessed by the area under the receiver operating characteristic curve (AUC-ROC) and calibration curves. Additionally, decision curve analysis was conducted to appraise the clinical utility of the nomogram. RESULTS: Our nomogram was derived from two clinical factors (ASPECT score and onset to reperfusion time) and two CT texture features ( variance and uniformity), with AUC-ROC of 0.943, 0.930 and 0.937 in the development, internal validation and external validation cohorts, respectively. Furthermore, the calibration plot exhibited a strong agreement between the predicted outcome and the actual outcome. In addition, the decision curve analysis revealed the clinical utility of the nomogram in accurately predicting hemorrhage in patients with PTIH. CONCLUSION: The developed nomogram, based on clinical factors and CT texture features, proves to be effective in distinguishing intracerebral hemorrhage from contrast extravasation in patients with PTIH.

Global, regional, and national temporal trends of diet-related ischemic stroke mortality and disability from 1990 to 2019.

BACKGROUND: Stroke is the second leading cause of death and the third leading cause of disability in the general population worldwide. However, the changing trend of ischemic stroke burden attributable to various dietary risk factors has not been fully revealed and may contribute to a better understanding of stroke epidemiology. AIMS: Our article aimed to evaluate the temporal trend of diet-related ischemic stroke burden to inform future research and policy-making. METHODS: This analysis was based on the data from the Global Burden of Disease (GBD) Study 2019 (spanning years 1990 to 2019), and we used the joinpoint regression to model temporal trends in diet-related ischemic stroke burden across countries and regions of the world during the study period. Six specific dietary factors known to influence stroke risk, including sodium, red meat, fiber, vegetables, whole grains, and fruits, were evaluated in the GBD study to determine their individual and joint impact on ischemic stroke. The changing trend was primarily measured by the average annual percent change (AAPC). Age-standardized rates (ASRs) of mortality and years lived with disability (YLD) per 100,000 population were used to evaluate disease burden. Finally, the socioeconomic background, which was quantified as sociodemographic index (SDI), and its association with diet-related ischemic stroke burden were also explored with the Pearson correlation coefficient. RESULTS: During the study period, the ischemic stroke ASR of mortality attributable to overall dietary risk decreased by an average of 1.6% per year, while the ASR of YLD decreased by an average of 0.2% per year. High sodium diet was still a key driver of diet-related ischemic stroke, accounting for 8.4% and 11.0% of deaths and disabilities, respectively, in 2019. In addition, we found a negative association between temporal evolution of stroke burden and socioeconomic background (r = -0.6603 for mortality and r = -0.4224 for disability, P < 0.001), which suggested that the developing countries with weak social and economic foundation faced greater challenges from the ongoing burden of diet-related strokes compared with developed countries. CONCLUSIONS: Our study found declining trends and revealed the current status of diet-related ischemic stroke mortality and disability. Interdisciplinary countermeasures involving the development of effective food policies, evidence-based guidelines, and public education are needed in the future to combat this global epidemic. DATA ACCESS STATEMENT: The data used for analysis were open-access and can be obtained from https://vizhub.healthdata.org/gbd-results/.

E2F1 Mediates Traumatic Brain Injury and Regulates BDNF-AS to Promote the Progression of Alzheimer's Disease.

Traumatic brain injury (TBI) is one of the important risk factors for the development of Alzheimer's disease (AD). However, the molecular mechanism by which TBI promotes the progression of AD is not elucidated. In this study, we showed that the abnormal production of E2F1 is a major factor in promoting the neuropathological and cognitive deterioration of AD post-TBI. We found that repeated mild TBI can aggravate the neuropathology of AD in APP/PS1 mice. At the same time, the co-expression of E2F1 and beta-site APP cleaving enzyme 1 (BACE1) was upregulated when the mouse hippocampus was dissected. BACE1 is recognized as a rate-limiting enzyme for the production of Aß. Here, we speculate that E2F1 may play a role in promoting BACE1 expression in AD. Therefore, we collected peripheral blood from patients with AD. Interestingly, there is a positive correlation between E2F1 and brain-derived neurotrophic factor-antisense (BDNF-AS), whereas BDNF-AS in AD can promote the expression of BACE1 and exhibit a neurotoxic effect. We established a cell model and found a regulatory relationship between E2F1 and BDNF-AS. Therefore, based on our results, we concluded that E2F1 regulates BDNF-AS, promotes the expression of BACE1, and affects the progression of AD. Furthermore, E2F1 mediates the TBI-induced neurotoxicity of AD.

Role of Lipocalin-2 in N1/N2 Neutrophil Polarization After Stroke.

BACKGROUND: Neutrophils and Lipocalin-2 (LCN2) play pivotal roles in cerebral ischemiareperfusion (I/R) injury. However, their contribution is not fully clarified. OBJECTIVE: This study aimed to explore the role of LCN2 and its association with neutrophil polarization in I/R injury. METHODS: A mouse model of middle cerebral artery occlusion (MCAO) was used to induce cerebral ischemia. LCN2mAb was administered 1 h and Anti-Ly6G was administered for 3d before MCAO. The role of LCN2 in the polarity transition of neutrophils was explored using an in vitro HL-60 cell model. RESULTS: LCN2mAb pretreatment had neuroprotective effects in mice. The expression of Ly6G was not significantly different, but the expression of N2 neutrophils was increased. In the in vitro study, LCN2mAb-treated N1-HL-60 cells induced N2-HL-60 polarization. CONCLUSION: LCN2 may affect the prognosis of ischemic stroke by mediating neutrophil polarization.

Optimum Baseline Clinical Severity Scale Cut Points for Prognosticating Intracerebral Hemorrhage: INTERACT Studies.

BACKGROUND: The optimal cut point of baseline National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale scores for prognosticating acute intracerebral hemorrhage (ICH) is unknown. METHODS: Secondary analyses of participant data are from the INTERACT (Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trials) 1 and 2 studies. Receiver operating characteristic analyses were used to compare the predictive performance of baseline NIHSS and Glasgow Coma Scale scores, ICH score, and max-ICH score. Optimal cut points for predicting 90-day clinical outcomes (death or major disability [defined as modified Rankin Scale scores 3-6], major disability [defined as modified Rankin Scale scores 3-5], and death alone) were determined using the Youden index. Logistic regression models were adjusted for age, sex, hematoma volume, and other known risk factors for poor prognosis. We validated our findings in the INTERACT1 database. RESULTS: There were 2829 INTERACT2 patients (age, 63.5±12.9 years; male, 62.9%; ICH volume, 10.96 [5.77-19.49] mL) included in the main analyses. The baseline NIHSS score (area under the curve, 0.796) had better prognostic utility for predicting death or major disability than the Glasgow Coma Scale score (area under the curve, 0.650) and ICH score (area under the curve, 0.674) and was comparable to max-ICH score (area under the curve, 0.789). Similar findings were observed when assessing the outcome of major disability. A cut point of 10 on baseline NIHSS optimally (sensitivity, 77.5%; specificity, 69.2%) predicted death or major disability (adjusted odds ratio, 4.50 [95% CI, 3.60-5.63]). The baseline NIHSS cut points that optimally predicted major disability and death alone were 10 and 12, respectively. The predictive effect of NIHSS≥10 for poor functional outcomes was consistent in all subgroups including age and baseline hematoma volume. Results were consistent when analyzed in the independent INTERACT1 validation database. CONCLUSIONS: In patients with mild-to-moderate ICH, a baseline NIHSS score of ≥10 was optimal for predicting poor outcomes at 90 days. Prediction based on baseline NIHSS is better than baseline Glasgow Coma Scale score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096 and NCT00716079.

Albumin-Globulin Ratio and Common Carotid Artery Intima-Media Thickness in Patients with Ischemic Stroke.

BACKGROUND: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS. METHODS: A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models. RESULTS: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P <0.01). CONCLUSION: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT.

Prognostic significance of plasma SDF-1 in acute ischemic stroke patients with diabetes mellitus: the CATIS trial.

BACKGROUND AND OBJECTIVES: Evidence on the associations between baseline stromal cell-derived factor (SDF)-1 and clinical outcomes in acute ischemic stroke patients is lacking. The present study aimed to examine the relationship between plasma SDF-1 levels and clinical outcomes based on a large multicenter study of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). METHODS: Secondary analysis was conducted among 3,255 participants from the CATIS trial with a baseline measurement of plasma SDF-1 levels. We evaluated the associations between plasma SDF-1 levels and one-year recurrent stroke, cardiovascular events, and all-cause mortality using Cox regression models. We further investigated the prognostic effect of SDF-1 on clinical outcomes in patients with different characteristics. RESULTS: Higher plasma SDF-1 levels were not associated with recurrent stroke, cardiovascular events, and all-cause mortality at one-year after ischemic stroke (all P trend ≥ 0.05). There were significant interactions between plasma SDF-1 levels and history of diabetes mellitus on recurrent stroke (P = 0.005), cardiovascular events (P = 0.007) and all-cause mortality (P = 0.04) at one year. In patients with diabetes mellitus, plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events after adjustment for confounders. For example, 1-SD higher log-SDF-1 was associated with a hazard ratio (95% confidence interval) of 1.65 (1.18-2.32) for recurrent stroke and 1.47 (1.08-1.99) for the cardiovascular events, but not all-cause mortality 1.36 (0.96-1.93) at one year. However, there were no associations between plasma SDF-1 and clinical outcomes in patients without diabetes mellitus (all P > 0.05). The addition of plasma SDF-1 to the conventional risk factors model significantly improved the risk prediction of all outcomes. Similarly, findings between elevated SDF-1 levels and two-year outcomes were found only in patients with diabetes mellitus. CONCLUSIONS: Elevated plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events only in ischemic patients with diabetes mellitus.

Prognostic significance of serum globulin in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: We investigated the association between serum globulin levels upon hospital admission and in-hospital short-term outcomes in acute ischemic stroke (AIS) patients. METHODS: A total of 3,127 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into 4 groups according to their level of admission serum globulin: Q1 (<23.5 g/L), Q2 (23.5-26.4 g/L), Q3 (26.4-29.9 g/L), and Q4 (≥29.9 g/L). Logistic regression models were used to estimate the effect of serum globulin on the short-term outcomes, including all cause in-hospital mortality, poor outcome upon discharge (modified Rankin Scale score ≥3) and in-hospital pneumonia in AIS patients. RESULTS: The median National Institutes of Health Stroke Scale (NIHSS) score was 4.0 (IQR, 2.0-7.0). The risk of in-hospital mortality was significantly higher in patients with highest serum globulin level (Q4) compared to those with lowest (Q1) (adjusted odds ratio [OR] 2.30; 95% confidence interval [CI], 1.12-4.70; P-trend =0.026). The highest serum globulin level (Q4) was associated with a 1.32-fold and 1.62-fold increase in the risk of poor outcome upon discharge (adjusted OR 1.32; 95% CI, 1.00-1.75; P-trend = 0.070) and in-hospital pneumonia (adjusted OR 1.62; 95% CI, 1.18-2.23; P-trend = 0.001) in comparison to Q1 after adjustment for potential covariates. CONCLUSIONS: A high level of serum globulin upon hospital admission was independently associated with all cause in-hospital mortality, poor outcome upon discharge and in-hospital pneumonia in relative mild AIS patients.

Prognostic Value of Red Blood Cell Distribution Width and Hemoglobin in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between baseline red blood cell distribution width (RDW) and hemoglobin levels and outcomes after acute intracerebral hemorrhage (ICH) is not well studied. We aimed to investigate the association between baseline RDW and hemoglobin levels with early hematoma expansion (HE) and mortality at 3 months and 1 year in acute ICH patients. METHODS: A total of 393 ICH patients from January 2014 to February 2019 were included. Patients were divided into four groups based on quartiles of RDW and hemoglobin levels at admission, respectively. Logistic regression models were used to estimate the effect of the levels of RDW and hemoglobin on early HE (absolute hematoma growth >6 mL from baseline to follow-up) and allcaused mortality at 3 months and 1 year. RESULTS: There were no significant associations between baseline RDW and hemoglobin levels and early HE. The 3-month mortality (adjusted odds ratio [OR] 2.88; 95% confidence intervals [CI] 0.96-8.64) and 1-year mortality (adjusted OR 3.16, 95% CI 1.08-9.21) was significantly higher in patients with the highest RDW level (Q4) compared to those with the lowest RDW level (Q1). Moreover, patients with the lowest hemoglobin level were significantly associated with increased odds of all-cause mortality at 3-month (adjusted OR 3.95, 95% CI 1.26-12.4) and 1-year (adjusted OR 4.42, 95% CI 1.56-12.5) compared to those with highest hemoglobin level. CONCLUSION: In patients with acute ICH, a higher level of RDW at admission significantly increased the risk of all-cause mortality at 1 year. Moreover, a decreased hemoglobin level at admission was also associated with a higher risk of all-cause mortality at 3 months and 1 year.

Headache disorders and relevant sex and socioeconomic patterns in adolescents and young adults across 204 countries and territories: an updated global analysis.

BACKGROUND: Primary headache disorders are a group of highly prevalent and disabling neurological diseases that mainly consist of migraine and tension-type headache (TTH). A previous study showed that the burden of headaches peaked at a working age that ranged from 15 to 49, particularly among females, affecting their productivity and severely damaging their social interactions. METHODS: The latest dataset was retrieved from the Global Burden of Disease (GBD) Study 2019. Three indicators, including prevalence, incidence, and years lived with disability (YLDs), were adopted for evaluation. The overall and specific headache burdens were fully compared and analysed at global, regional, and national levels. The ratio of female YLD rates to male YLD rates due to headaches was calculated to estimate the sex pattern. Finally, we utilized the two-tailed Spearman test to explore the potential association between socioeconomic background and headaches among young people. RESULTS: Globally, for overall headache disorders, a total of 2,049,979,883 prevalent cases (95% uncertainty interval (UI): 1,864,148,110 to 2,239,388,034), 601,229,802 incident cases (95% UI: 530,329,914 to 681,007,934), and 38,355,993 YLDs (95% UI: 7,259,286 to 83,634,503) were observed for those aged 10 to 54 in 2019. Sex differences were widely found for all headache types among adolescents and young adults, especially migraine. However, the most interesting finding was that the associations we tested between the socioeconomic environment and young headache patients were positive, regardless of region or specific country or territory. CONCLUSIONS: Overall, the global burden of headaches in adolescents and young adults largely increased from 1990 to 2019. Although slight declines were observed in sex differences, they remained significant and challenging. The positive correlations between headache and socioeconomic background among young people were relatively inconsistent with previous investigations, and several related hypotheses were proposed for explanation. Interdisciplinary actions involving education, policy- and law-making, and basic medical practice are desperately needed to further fight against the headache burden, promote gender equality in headache care, and eliminate the stigmatization of headache patients in student and working groups.

Integrating animal experiments, mass spectrometry and network-based approach to reveal the sleep-improving effects of Ziziphi Spinosae Semen and γ-aminobutyric acid mixture.

BACKGROUND: Ziziphi Spinosae Semen (ZSS) is a plant widely used as medicine and food in Asian countries due to its numerous health benefits. γ-aminobutyric acid (GABA), a non-proteinaceous amino acid, is one of the major inhibitory neurotransmitters with a relaxant function. In this study, a system pharmacology approach was employed to assess the effects of a mixture composed of ZSS and GABA (ZSSG) on sleep improvement. METHODS: Mice were divided into five groups (n = 10) and received either no treatment, sodium pentobarbital, or sodium barbital with diazepam or ZSSG. The effects of ZSSG on sleep quality were evaluated in mice, and differential metabolites associated with sleep were identified among the control, ZSS, GABA, and ZSSG groups. Additionally, network-based ingredient-insomnia proximity analysis was applied to explore the major ingredients. RESULTS: ZSSG significantly improved sleep quality by decreasing sleep latency and prolonging sleep duration in sodium pentobarbital-induced sleeping mouse model (P < 0.05). ZSSG significantly enhanced the brain content of GABA in mice. Furthermore, ZSSG also significantly decreased sleep latency-induced by sodium barbital in mice (P < 0.05). Metabolic analysis revealed significant differences in 10 metabolites between ZSSG group and the groups administering ZSS or GABA. Lastly, using the network-based ingredient screening model, we discovered potential four active ingredients and three pairwise ingredient combinations with synergistic effect on insomnia from ZSSG among 85 ingredients identified by UPLC-Q/TOF-MS. Also, we have constructed an online computation platform. CONCLUSION: Our data demonstrated that ZSSG improved the sleeping quality of mice and helped to balance metabolic disorders-associated with sleep disorders. Moreover, based on the network-based prediction method, the four potential active ingredients in ZSSG could serve as quality markers-associated with insomnia. The network-based framework may open up a new avenue for the discovery of active ingredients of herbal medicine for treating complex chronic diseases or symptoms, such as insomnia.

Aqueous extract of Polygala japonica Houtt. ameliorated nonalcoholic steatohepatitis in mice through restoring the gut microbiota disorders and affecting the metabolites in feces and liver.

BACKGROUND: Polygala japonica Houtt. (PJ) has been demonstrated with several biological potentials such as lipid-lowering and anti-inflammatory effects. However, the effects and mechanisms of PJ on nonalcoholic steatohepatitis (NASH) remain unclear. PURPOSE: The aim of this study was to evaluate the effects of PJ on NASH and illustrate the mechanism based on modulating gut microbiota and host metabolism. MATERIALS AND METHODS: NASH mouse model was induced using methionine and choline deficient (MCD) diet and orally treated with PJ. The therapeutic, anti-inflammatory, and anti-oxidative effects of PJ on mice with NASH were firstly assessed. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of PJ on the metabolites in liver and feces were explored by untargeted metabolomics. RESULTS: The results indicated that PJ could improve hepatic steatosis, liver injury, inflammatory response, and oxidative stress in NASH mice. PJ treatment also affected the diversity of gut microbiota and changed the relative abundances of Faecalibaculum. Lactobacillus, Muribaculaceae, Dubosiella, Akkermansia, Lachnospiraceae_NK4A136_group, and Turicibacter in NASH mice. In addition, PJ treatment modulated 59 metabolites both in liver and feces. Metabolites involved in histidine, and tryptophan metabolism pathways were identified as the key metabolites according to the correlation analysis between differential gut microbiota and metabolites. CONCLUSION: Our study demonstrated the therapeutic, anti-inflammatory and anti-oxidative potentials of PJ on NASH. The mechanisms of PJ treatment were related to the improvement of gut microbiota dysbiosis and the regulation of histidine and tryptophan metabolism.

Combined Role of Inflammatory Biomarkers and Red Blood Cell Distribution Width in Predicting In-hospital Outcomes of Acute Ischemic Stroke Patients Undergoing Thrombolysis.

BACKGROUND: To investigate the combined effect of red blood cell distribution width (RDW) and inflammatory biomarkers on in-hospital outcomes of acute ischemic stroke(AIS) patients with thrombolysis. METHODS: 417 AIS patients with thrombolysis were included. The participants were divided into four groups according to the cut-off of white blood cell (WBC) or C reactive protein (CRP) and RDW: LWLR, LWHR, HWLR, and HWHR; or LCLR, LCHR, HCLR, and HCHR (L-low, Hhigh, W-WBC, C-CRP, R-RDW). Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of in-hospital pneumonia and functional outcome across the four subgroups. RESULTS: Patients with higher RDW and inflammatory biomarkers levels have the highest risk of in-hospital outcomes. Compared with patients in the LWLR group, the ORs (95% CIs) of those in the HWHR group were 12.16 (4.21-35.14) and 9.31 (3.19-27.17) for in-hospital pneumonia and functional outcome. The ORs (95% CIs) of those in the HCHR group were 6.93 (2.70-17.78) and 3.38 (1.10-10.39) for in-hospital pneumonia and functional outcome, compared with patients in the LCLR group. Simultaneously adding RDW and WBC or CRP to the basic model with established risk factors significantly improved risk discrimination and reclassification for pneumonia and functional outcome (all p <0.05). CONCLUSIONS: Combined RDW and inflammatory biomarkers within 4.5 hours had a better predictive power for in-hospital outcomes of AIS patients with thrombolysis.

Effect of the interaction between atrial fibrillation and rt-PA dose on the prognosis of acute ischaemic stroke with intravenous thrombolysis.

BACKGROUND: The association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood. METHODS: Patients who had an AIS were enrolled from eight stroke centres in China. According to the recombinant tissue plasminogen activator dose, patients treated with intravenous recombinant tissue plasminogen activator within 4.5 hours after symptom onset were divided into a low-dose group (recombinant tissue plasminogen activator <0.85 mg/kg) and a standard-dose group (recombinant tissue plasminogen activator ≥0.85 mg/kg). Patients who had an AIS in the low-dose group and the standard dose group were divided into whether or not they had AF. The main outcomes were major disability (modified Rankin scale (mRS) score 3-5), mortality and vascular events occurring within 3 months. RESULTS: The study included 630 patients who received recombinant tissue plasminogen activator after AIS, including 391 males and 239 females, with a mean age of 65.8 years. Of these patients, 305 (48.4%) received low-dose recombinant tissue plasminogen activator and 325 (51.6%) received standard dose recombinant tissue plasminogen activator. The recombinant tissue plasminogen activator dose significantly influenced the association between AF and death or major disability (p-interaction=0.036). After multivariate adjustment, AF was associated with an increased risk of death or major disability (OR 2.90, 95% CI 1.47 to 5.72, p=0.002), major disability (OR 1.93, 95% CI 1.04 to 3.59, p=0.038) and vascular events (HR 5.01, 95% CI 2.25 to 11.14, p<0.001) within 3 months in patients with standard-dose recombinant tissue plasminogen activator. No significant association was found between AF and any clinical outcome in patients with low-dose recombinant tissue plasminogen activator (all p>0.05). With AF, the mRS score distribution showed a significantly worse shift in patients with standard-dose recombinant tissue plasminogen activator (p=0.016) than in those with low-dose recombinant tissue plasminogen activator (p=0.874). CONCLUSIONS: AF may be a strong predictor of poor prognosis in patients who had an AIS receiving standard-dose recombinant tissue plasminogen activator, suggesting that low-dose recombinant tissue plasminogen activator should be administered to patients who had a stroke with AF to improve their prognosis.

The prognostic value of deep earlobe creases in patients with acute ischemic stroke.

Background and purpose: Data on earlobe crease (ELC) among patients with acute ischemic stroke (AIS) are limited. Here, we determined the frequency and characteristics of ELC and the prognostic effect of ELC among AIS patients. Methods: A total of 936 patients with acute AIS were enrolled during the period between December 2018 and December 2019. The patients were divided into those without and with ELC, unilateral and bilateral ELC, and shallow and deep ELC, according to the photographs taken of the bilateral ears. Logistic regression models were used to estimate the effect of ELC, bilateral ELC, and deep ELC on poor functional outcomes at 90 days (a modified Rankin Scale score ≥2) in AIS patients. Results: Among the 936 AIS patients, there were 746 (79.7%) patients with ELC. Among patients with ELC, there were 156 (20.9%) patients with unilateral ELC and 590 (79.1%) with bilateral ELC and 476 (63.8%) patients with shallow ELC and 270 (36.2%) with deep ELC. After adjusting for age, sex, baseline NIHSS score, and other potential covariates, patients with deep ELC were associated with a 1.87-fold [odds ratio (OR) 1.87; 95% confidence interval (CI), 1.13-3.09] and 1.63-fold (OR 1.63; 95%CI, 1.14-2.34) increase in the risk of poor functional outcome at 90 days in comparison with those without ELC or shallow ELC. Conclusion: ELC was a common phenomenon, and eight out of ten AIS patients had ELC. Most patients had bilateral ELC, and more than one-third had deep ELC. Deep ELC was independently associated with an increased risk of poor functional outcome at 90 days.

Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients.

BACKGROUND: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients. METHODS: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients. RESULTS: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge. CONCLUSIONS: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

Podoplanin: A potential therapeutic target for thrombotic diseases.

As a specific lymphatic marker and a key ligand of C-type lectin-like receptor 2 (CLEC-2), podoplanin (Pdpn) is involved in various physiological and pathological processes such as growth and development, respiration, blood coagulation, lymphangiogenesis, angiogenesis, and inflammation. Thrombotic diseases constitute a major cause of disability and mortality in adults, in which thrombosis and inflammation play a crucial role. Recently, increasing evidence demonstrates the distribution and function of this glycoprotein in thrombotic diseases such as atherosclerosis, ischemic stroke, venous thrombosis, ischemic-reperfusion injury (IRI) of kidney and liver, and myocardial infarction. Evidence showed that after ischemia, Pdpn can be acquired over time by a heterogeneous cell population, which may not express Pdpn in normal conditions. In this review, the research progresses in understanding the roles and mechanisms of podoplanin in thromobotic diseases are summarized. The challenges of podoplanin-targeted approaches for disease prognosis and preventions are also discussed.