Intracerebral hemorrhage-induced brain injury in mice: The role of peroxiredoxin 2-Toll-like receptor 4 inflammatory axis.

BACKGROUND: Peroxiredoxin 2 (Prx2), an intracellular protein that regulates redox reactions, released from red blood cells is involved in inflammatory brain injury after intracerebral hemorrhage (ICH). Toll-like receptor 4 (TLR4) may be crucial in this process. This study investigated the role of the Prx2-TLR4 inflammatory axis in brain injury following experimental ICH in mice. METHODS: First, C57BL/6 mice received an intracaudate injection of autologous arterial blood or saline and their brains were harvested on day 1 to measure Prx2 levels. Second, mice received an intracaudate injection of either recombinant mouse Prx2 or saline. Third, the mice were co-injected with autologous arterial blood and conoidin A, a Prx2 inhibitor, or vehicle. Fourth, the mice received a Prx2 injection and were treated with TAK-242, a TLR4 antagonist, or saline (intraperitoneally). Behavioral tests, magnetic resonance imaging, western blot, immunohistochemistry/immunofluorescence staining, and RNA sequencing (RNA-seq) were performed. RESULTS: Brain Prx2 levels were elevated after autologous arterial blood injection. Intracaudate injection of Prx2 caused brain swelling, microglial activation, neutrophil infiltration, neuronal death, and neurological deficits. Co-injection of conoidin A attenuated autologous arterial blood-induced brain injury. TLR4 was expressed on the surface of microglia/macrophages and neutrophils and participated in Prx2-induced inflammation. TAK-242 treatment attenuated Prx2-induced inflammation and neurological deficits. CONCLUSIONS: Prx2 can cause brain injury following ICH through the TLR4 pathway, revealing the Prx2-TLR4 inflammatory axis as a potential therapeutic target.

Clinical significance of the Microbleed Anatomical Rating Scale score in ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: Conflicting results were shown on the relationship between cerebral microbleeds (CMBs) burden and functional outcomes in patients treated with intravenous tissues plasminogen activator (IV tPA). We aimed to investigate the relationship between CMBs burden and functional outcomes using the Microbleed Anatomical Rating Scale (MARS) and determine its optimal cutoff value. METHODS: A retrospective study was conducted to include patients treated with IV tPA in our stroke center, and the MARS was used to assess the CMBs burden. Other clinical data including demographic factors, stroke severity, vascular risk factors, and clinical outcomes were also documented. Another mediation analysis was performed to investigate whether early neurological improvement could mediate the association between MARS and functional outcomes. RESULTS: A total of 408 patients were included. A cutoff value of 1.5 could predict functional outcomes in patients treated with IV tPA. Based on that cutoff value, MARS showed an independent relationship with functional outcomes [adjusted OR (Odds Ratio) 0.841, 95% confidence interval (CI) 0.720-0.982, P = .029]. A shift analysis showed that higher MARS score (MARS ≥1.5) was related with poor functional outcome according to mRS score distribution (OR = 0.519, 95% CI 0.336-0.803, P = .003). Total effect (indirect + direct effect) was calculated and showed in figure. Early neurological improvement mediated 24% of the effect of MARS score on functional outcomes. CONCLUSION: Our study showed that MARS could be a potential method to assess the functional outcome based on CMBs in patients treated with IV tPA, and MARS score ≥ 1.5 might be an optimal threshold for poor functional outcome.

Tenecteplase versus alteplase for acute ischaemic stroke: a meta-analysis of phase III randomised trials.

BACKGROUND: Tenecteplase (TNK) was found non-inferior to alteplase in recent clinical trials. We aimed to elucidate the efficacy and safety of TNK versus alteplase for acute ischaemic stroke (AIS). METHODS: Systematic literature search and a meta-analysis of phase III clinical trials in ischaemic stroke patients with TNK use were conducted. The primary outcome was excellent functional outcome which was defined as modified Rankin Scale score of 0-1 at 90 days and safety outcomes included symptomatic intracerebral haemorrhage and death at 90 days. We used random-effects model to estimate the pooled risk difference and 95% CI in R package 'Meta'. The included trials were adapted to the non-inferiority analysis with a margin of -4%. RESULTS: Three trials enrolling 4094 patients were identified by systematic search. All trials included AIS patients within 4.5 hours time window. Meta-analysis indicated that 1089 (53.0%) of 2056 patients in the TNK arm and 1016 (50.5%) of 2012 in the alteplase arm had excellent functional outcome at 90 days (0.03 (95% CI -0.00 to 0.06); I2=0%), meeting the prespecified non-inferiority threshold. And TNK thrombolysis was not correlated with increased risk of symptomatic intracerebral haemorrhage (0.00 (95% CI -0.01 to 0.01); I2=0%) or death (0.01 (95% CI -0.01 to 0.02); I2=0%) at 90 days. The sensitivity analysis with the 0.25 mg/kg trials exclusively showed similar results to the main analysis. CONCLUSIONS: TNK was non-inferior to alteplase for achieving excellent functional outcome at 90 days without increasing the safety concern in treating patients with AIS. These findings suggest that TNK can be an alternative to alteplase. PROSPERO REGISTRATION NUMBER: CRD42022354342.

Intravenous thrombolysis for acute ischemic stroke during two COVID-19 outbreaks in China: Wuhan pandemic and Beijing pandemic.

INTRODUCTION: The COVID-19 pandemic has had an impact on the emergency department (ED). Door-to-needle time (DNT) could be prolonged for intravenous thrombolysis (IVT) treatment. We aimed to investigate the impact of two COVID-19 pandemics on the workflow of IVT in our neurovascular ED. METHOD: We performed a retrospective analysis of patients who received IVT treatment in the neurovascular ED of Beijing Tiantan Hospital, Beijing, from January 20, 2020, to October 30, 2020, covering two COVID-19 pandemics in China. The time-based performances of IVT treatment including onset-to-arrival time, arrival-to-CT time, CT-to-needle time, door-to-needle time, and onset-to-needle time were recorded. Data on clinical characteristics and imaging information were also collected. RESULTS: Four hundred forty patients that received IVT were enrolled in this study. The number of patients admitted to our neurovascular ED began to decrease in December 2019 and was the lowest in April 2020 (n = 95). Longer DNT (Wuhan pandemic: 49.00 [35.00, 64.00] min; Beijing pandemic: 55.00 [45.50, 77.00] min) interval delays were observed during the two pandemics (p = .016). More patients admitted during the two pandemics had an 'unknown' subtype (Wuhan pandemic: 21.8%; Beijing pandemic: 31.4%. p = .008). The percentage of the cardiac embolism subtype was higher during the Wuhan pandemic (20.0%) than during other periods. The median admission NIHSS score increased during the Wuhan pandemic and the Beijing pandemic (8.00 [4.00, 12.00], 7.00 [4.50, 14.00], respectively, p < .001). CONCLUSION: The number of patients who received IVT decreased during the Wuhan pandemic. Higher admission NIHSS scores and prolonged DNT intervals were also observed during the Wuhan pandemic and the Beijing pandemic.

Intravenous thrombolysis for mild stroke: NIHSS 3-5 Versus NIHSS 0-2.

BACKGROUND AND PURPOSE: Studies have shown that mild stroke patients with National Institutes of Health Stroke Scale (NIHSS) score 3-5 but not 0-2 may benefit from the intravenous thrombolysis when compared with antiplatelet therapy. We aimed to compare the safety and effectiveness of thrombolysis in mild stroke with NIHSS score of 0-2 vs. 3-5 and identify the predictors of an excellent functional outcome in a real world longitudinal registry. METHODS: In a prospective thrombolysis registry, we identified patients with acute ischemic stroke who presented within 4.5 hours of symptom onset and had initial NIHSS scores ≤ 5. Demographic data, medical history, pre-stroke medications, imaging data, and laboratory measures were collected. The outcome of interest was modified Rankin Scale score of 0 to 1 at discharge. Safety outcome was evaluated by syptomatic intracrerebral hemorrhage defined as any decline in neurologic status due to hemorrhage within 36 h. Multivariable regression models were performed to explore the safety and effectiveness in the alteplase-treated patients with admission NIHSS 0-2 vs. 3-5 and identify factors independently associated with an excellent functional outcome. RESULTS: Of a total of 236 eligible patients, those with an admission NIHSS score of 0-2 (n=80) had a better functional outcome at discharge compared with NIHSS 3-5 group (n=156) (81.3% vs. 48.7%, adjusted odds ratio [aOR] 0.40, 95% confidential interval [CI] 0.17 - 0.94, P=0.04) without increasing the rate of symptomatic intracerebral hemorrhage and mortality. Non-disabling stroke (Model 1: aOR 0.06, 95%CI 0.01-0.50, P=0.01; Model 2: aOR 0.06, 95% CI 0.01-0.48, P=0.01) and prior statin therapy (Model 1: aOR 3.46, 95% CI 1.02-11.70, P=0.046; Model 2: aOR 3.30, 95% CI 0.96-11.30, P=0.06) were independent predictors of excellent outcomes. CONCLUSIONS: Acute ischemic stroke patients with admission NIHSS 0-2 was associated with better functional outcomes at discharge compared with NIHSS 3-5 within the 4.5-hour time window. Minor stroke severity, non-disabling stroke and prior statin therapy were independent predictors for funcitonal outcomes at discharge. Further studies with large sample size are needed to confirm the findings.

Prognostic Value of Stress Hyperglycaemia Ratio in Young Patients with Ischaemic Stroke or Transient Ischaemic Attack.

INTRODUCTION: Stress hyperglycaemia is common in stroke. Recently, the stress hyperglycaemia ratio (SHR) has been proposed as a novel marker for stress hyperglycaemia and found to be associated with adverse outcomes in many diseases. However, data regarding the impact of the SHR on ischaemic stroke, especially in young adults, are limited. Therefore, the aim of this study was to investigate whether the SHR is associated with stroke severity and adverse outcomes in young adults with ischaemic stroke or transient ischaemic attack (TIA). METHODS: We retrospectively recruited patients aged 18-45 years with acute ischaemic stroke or TIA. The SHR was calculated as fasting blood glucose (FBG) divided by glycated haemoglobin. The primary and secondary outcomes were 90-day poor functional outcomes and stroke severity on admission, respectively. Multivariable logistic regression, restricted cubic spline models, and subgroup analysis were performed to validate the relationship between the SHR and ischaemic stroke or TIA in young adults. RESULTS: A total of 687 young adults (mean age 36.9 years) were recruited. Among them, 119 (17.3%) patients had prior diabetes, and 568 (82.7%) did not. The SHR was significantly associated with stroke severity and poor functional outcome. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have moderate-to-severe stroke. The multivariable-adjusted OR (95% CI) was 1.70 (1.21-2.39) after adjusting for all potential confounders excluding FBG and 1.50 (1.03-2.17) after FBG adjustment. The restricted cubic spline showed a J-shaped association between the SHR and moderate-to-severe stroke. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have poor functional outcome at 90-day follow-up. The multivariable-adjusted OR (95% CI) was 1.95 (1.12-3.41) after adjusting for all potential confounders excluding FBG and 1.84 (1.01-3.36) after FBG adjustment. A J-shaped association was found between the SHR and poor functional outcomes at the 90-day follow-up. In the subgroup analysis, SHR was independently associated with more severe stroke (OR, 1.79, 95% CI, 1.18-2.72) and poor functional outcomes (OR, 2.11, 95% CI, 1.32-3.35) in nondiabetic patients but not in diabetic patients in multivariate logistic analysis. Despite this, the interaction effects of prior diabetes on the association between the SHR and stroke severity and poor functional outcomes did not reach statistical significance. CONCLUSION: The SHR is independently related to more severe stroke and an increased risk of poor functional outcomes among young adults with ischaemic stroke or TIA.

Clinical Significance of Stress Hyperglycemic Ratio and Glycemic Gap in Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

Objective: The clinical significance of different glycemic parameters has been rarely investigated in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). This study was aimed to investigate the association between different glycemic parameters and favorable functional outcome in patients treated with IV tPA. Methods: Patients with ischemic stroke who received IV tPA therapy at our stroke center were retrospectively enrolled. Four glycemic parameters were collected including admission glucose, HbA1c, stress hyperglycemia ratio (SHR) and glycemic gap (GG). Additional information was also recorded including demographics, medical history, stroke severity, imaging measures and mRS score at discharge. We used 5 machine learning models to investigate the predictive value of glycemic parameters. Results: Our study included 294 patients treated with IV tPA. SHR and GG were independently associated with favorable functional outcome (adjusted OR for SHR 0.03, 95% CI 0.01-0.72, P = 0.03; adjusted OR for GG 1.024, 95% CI 1.00-1.05, P = 0.04). Conclusion: SHR and GG were associated with functional outcomes in acute ischemic stroke patients with intravenous thrombolysis.

Clinical significance of neutrophil to lymphocyte ratio in ischemic stroke and transient ischemic attack in young adults.

OBJECTIVE: Few studies evaluated the association between neutrophil to lymphocyte ratio (NLR) and clinical outcomes in ischemic stroke or transient ischemia attack (TIA) in young adults. We aimed to investigate the relationship of NLR with 90-day functional independence in ischemic stroke or TIA in young adults. METHODS: We retrospectively included patients aged 18-45 and diagnosed with ischemic stroke or TIA. Information including demographics, clinical and imaging characteristics, and the 90-day clinical outcome was collected. The primary outcome was excellent clinical outcome at 90 days, defined as mRS 0-1. Logistic regression analyses and a receiver operator characteristic (ROC) curve were used to investigate the association between NLR and 90-day clinical outcome. RESULTS: A total of 691 young patients with ischemic stroke or TIA were included in the final study. A higher level of NLR indicated poorer clinical outcome at 90 days (p for trend <0.001). The multivariable logistics regression suggested that NLR was an independent predictor of mRS 0-1 at 90 days (crude OR: 0.88, 95% CI 0.83-0.94, p < 0.001; adjusted OR of model 2: 0.87, 95% CI 0.84-0.94, p < 0.001; adjusted OR of model 3: 0.92, 95% CI 0.84-0.99, p = 0.04). CONCLUSION: In our study, a higher level of NLR was correlated with poorer functional outcomes at 90 days in ischemic stroke or TIA in young adults.

Uric Acid and Clinical Outcomes in Young Patients with Ischemic Stroke.

Background and Purpose: There is limited available evidence for the relationship between uric acid (UA) levels and ischemic stroke in young adults. We aimed to explore the association between UA levels and acute ischemic stroke (AIS) in young patients. Materials and Methods: This was a prospective and observational study. We recruited young patients aged 18-45 years with AIS at our tertiary hospital. Patients were categorized into four groups according to quartiles of UA levels. The primary outcome was functional outcome at 3 months. The secondary outcomes included stroke severity, in-hospital complications, and functional outcome at discharge. Modified Rankin Scale (mRS) scores were used to assess functional outcome as poor (mRS=2-6) or favorable(mRS=0-1). Results: A total of 636 patients were enrolled in the current analysis. The four groups were defined as follows: Q1≤289.8 µmol/L, 289.8 µmol/ L421 µmol/L. Multiple logistic regression analysis showed that UA levels were not significantly predictive of functional outcome either at discharge or at 3 months after AIS. However, compared to Q1, higher UA levels were significantly negatively associated with the rate of moderate-severe stroke (NIHSS≥5) at admission (p for trend =0.016). Furthermore, a reduction in the risk for in-hospital pneumonia was significantly associated with higher UA levels compared to Q1 (P for trend < 0.0001). Conclusion: Serum UA was a protective factor for stroke severity and in-hospital pneumonia after AIS in young patients. However, we were unable to identify the predictive significance of UA for functional outcome either at discharge or at 3 months after AIS.

Evaluation of Diffusion-Perfusion Mismatch in Acute Ischemic Stroke with a New Automated Perfusion-Weighted Imaging Software: A Retrospective Study.

INTRODUCTION: The aim of this study was to evaluate the accuracy of automated software (iStroke) on magnetic resonance (MR) apparent diffusion coefficient (ADC) and perfusion-weighted imaging (PWI) against ground truth in assessing infarct core, and compare the hypoperfusion volume and mismatch volume on iStroke with those on Food and Drug Administration-approved software (RAPID) in patients with acute ischemic stroke. METHODS: We used the single-volume decomposition method to develop the iStroke (iStroke; Beijing Tiantan Hospital, Beijing, China) software. Patients with ischemic stroke were collected from two educational hospitals in China with MR-PWI performed in the emergency department within 24 h of symptom onset. Infarct core volume was defined as ADC < 620 × 10-6 mm2/s and hypoperfusion volume was defined as Tmax > 6 s. We compared the accuracy of infarct core volume using iStroke and RAPID (iSchema View Inc, Menlo Park, CA) software with ground truth. RESULTS: We included 405 patients with acute ischemic stroke with MR ADC and PWI sequences. The infarct core volume on iStroke (median 2.43 ml, interquartile range [IQR] 0.60-10.32 ml) was not significantly different from the ground truth (median 2.89 ml, IQR 0.77-9.17 ml) (P = 0.07); Bland-Altman curves showed that the core volume of iStroke and RAPID software were comparable with each other on individual agreement with ground truth. The hypoperfusion volume and mismatch volume on iStroke were not statistically different from those on the RAPID software, respectively. In patients with large vessel occlusion (n = 74), the agreement between iStroke and RAPID was substantial (kappa = 0.76) according to DEFUSE 3 criteria (infarct core < 70 ml, mismatch volume ≥ 15 ml, and mismatch ratio ≥ 1.8). CONCLUSIONS: The iStroke automatic processing of ADC and PWI is a reliable software for the identification of diffusion-perfusion mismatch in acute ischemic stroke.

Association Between Neutrophil-to-Lymphocyte Ratio/Lymphocyte-to-Monocyte Ratio and In-Hospital Clinical Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

Objective: Investigations on neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with ischemic stroke are insufficient. We aimed to investigate the relationship of NLR and LMR with in-hospital clinical outcomes at different time points in ischemic stroke patients treated with intravenous tissues plasminogen activator (IV tPA). Methods: We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. Demographics, clinical characteristics, imaging measures, and the in-hospital clinical outcomes including early neurological improvement (ENI, defined as NIHSS score reduction within 24 hours ≥4 points or decreased to the baseline) and favorable functional outcome (defined as modified Rankin scale 0-1) were collected. Multivariable logistic regression analyses were performed to test whether NLR or LMR was an independent predictor for the in-hospital clinical outcomes. Results: One hundred and two patients treated with IV tPA were included. NLR at 24 hours proved to be an independent predictor of ENI (adjusted OR=0.85, 95% CI=0.75-0.95, P=0.04). NLR at 48 hours and LMR at 48 hours proved to be independent predictors of mRS 0-1 at discharge (NLR at 48 hours: adjusted OR=0.64, 95% CI=0.49-0.83, P=0.01; LMR at 48 hours: adjusted OR=1.50, 95% CI=1.08-2.09, P=0.02). The AUC of NLR at 48 hours to predict favorable functional outcome at discharge was 0.79 (95% CI=0.70-0.88, P<0.001) and the optimal cut-off was 5.69 (sensitivity=0.52, specificity=0.63). Conclusion: In our study, NLR at 24 hours was correlated with ENI. Both NLR and LMR at 48 hours were closely associated with favorable functional outcomes at discharge.

In-hospital clinical outcomes in diffusion weighted imaging-negative stroke treated with intravenous thrombolysis.

OBJECTIVE: We aimed to investigate whether negative diffusion weighted imaging (DWI) is related to the in-hospital clinical outcomes for ischemic stroke patients with intravenous tissues plasminogen activator (IV tPA). METHODS: We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. The classification of DWI-positive or negative was based on post-IV tPA MR scan. Demographic factors, stroke characteristics, imaging information, and the in-hospital clinical outcomes including early neurological improvement (ENI) and favourable functional outcome were collected. Multivariable logistic regression and sensitivity analyses were conducted to test whether negative DWI imaging was an independent predictor of the in-hospital clinical outcomes. RESULTS: In the final study population, 437 patients treated with IV tPA were included and 12.36% of them had negative DWI imaging at the first MR scan post IV tPA. In the DWI-negative group, 51.9% (28/54) of the patients achieved ENI at 24 hours and 74.1% (40/54) of the patients achieved favourable clinical outcome at discharge. DWI-negative was not related to ENI (adjusted odds ratio 0.93, 95% confidence interval 0.17-4.91) or favourable clinical outcome (adjusted odds ratio 2.40, 95% confidence interval 0.48-11.95). Additional sensitivity analyses yielded similar results. CONCLUSION: DWI-negative is not associated with ENI or favourable functional outcome at discharge.

Higher fasting blood glucose was associated with worse in-hospital clinical outcomes in patients with primary intracerebral hemorrhage: From a large-scale nationwide longitudinal registry.

INTRODUCTION: Studies that investigated the relationship between fasting blood glucose (FBG) and intracerebral hemorrhage (ICH) outcomes were insufficient. AIM: We aimed to investigate the association between FBG level and in-hospital clinical outcomes in patients with primary ICH. RESULTS: A total of 34,507 patients were enrolled in the final study. Compared with the reference group, the ≥6.1 and <7 mmol/L group showed nonsignificant higher in-hospital mortality (adjusted odds ratio [OR] 1.20, 95% confidence interval [CI] 0.69-2.11, p = 0.52), and a significant higher proportion of intracranial hematoma evacuation (adjusted OR 1.56, 95% CI 1.26-1.92, p < 0.001). The ≥7 mmol/L group showed both significant higher in-hospital mortality (adjusted OR 2.08, 95% CI 1.42-3.04, p = 0.52) and a significant higher proportion of intracranial hematoma evacuation (adjusted OR 2.09, 95% CI 1.78-2.47, p < 0.001). CONCLUSION: Higher FBG level was correlated with both higher mortality and proportion of evacuation of intracranial hematoma.

Impact of serum phosphate on severity and functional outcomes after ischemic stroke in young adults.

BACKGROUND AND AIMS: Serum phosphate is an essential nutrient that plays multiple physiological roles in cardiovascular function. The aim of this study was to investigate the association between serum phosphate and stroke severity and prognosis in ischemic stroke and transient ischemic attack (TIA) among young adults. METHODS AND RESULTS: We retrospectively recruited patients with acute ischemic stroke and TIA aged 18-45 years. The primary outcome was 90-day poor functional outcome (modified Rankin Scale score of 2-6). The secondary outcomes included stroke severity (NIHSS ≥5 was defined as moderate to severe stroke) and poor functional outcome at hospital discharge. A total of 687 patients with a mean age of 36.8 years were enrolled. Lower serum phosphate levels were significantly associated with more severe stoke (P for trend = 0.017). Compared with the fourth quartile, the odds ratio (95% CI) of the first quartile was 1.85 (1.19-3.22) for moderate to severe stroke. After adjusting for confounders other than stroke severity, the odds ratio (95% CI) of the first quartile was 1.74 (1.06-2.86) for poor functional outcome at hospital discharge and 1.90 (1.09-3.31) at 90-day follow-up compared with the fourth quartile. However, the significant association between serum phosphate and poor functional outcomes disappeared after stroke severity was further adjusted. CONCLUSIONS: Serum phosphate is more likely a marker of stroke severity than a contributor to poor functional outcomes after ischemic stroke and TIA in young adults. Lower serum phosphate levels were associated with more severe stroke.

Clinical Significance and Dynamic Change of Coagulation Parameters in Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

OBJECTIVE: Investigations on coagulation parameters including fibrinogen (Fbg), fibrinogen degradation products (FDP), and D-dimer in ischemic stroke patients treated with intravenous thrombolysis are insufficient. We aimed to investigate the association between in-hospital clinical outcomes and the coagulation parameters at different time points in ischemic stroke patients treated with intravenous tissues plasminogen activator (IV tPA). METHODS: We retrospectively enrolled patients who received IV tPA therapy within 4.5 h from symptoms onset. Demographics, clinical characteristics, imaging measures, and the discharge mRS score were collected. Multivariable logistic regression analyses were performed to test whether coagulation parameters were independent predictors for the in-hospital clinical outcomes. We also employed machine learning models to investigate whether coagulation parameters were able to improve the prediction of favorable functional outcomes. RESULTS: One hundred and fifty-two patients treated with IV tPA were included. Among the coagulation parameters, low D-dimers at 48 h proved to be an independent predictor of favorable functional outcome (adjusted odd ratio 0.24, 95% confidential intervals 0.06-0.92, P = 0.04). The AUC of D-dimer at 48 h to predict favorable functional outcome was 0.73 (0.60-0.87) and the optimal cut-off value was 0.92 (sensitivity 0.69, specificity 0.78). Machine learning models with D-dimer at 48 h had superior performance in predicting favorable functional outcomes and among the input variables in the machine learning models, D-dimer at 48 h showed the highest weight in predicting mRS 0-1 at discharge (38.44%). CONCLUSION: Increased levels of D-dimer at 48 h was associated with lower proportion of favorable functional outcomes in acute ischemic stroke patients with intravenous thrombolysis.

Prognostic value of glycemic gap in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Glycemic gap (GG), as a novel biomarker showing the acute glycemic change after the onset of acute illness, has been found to be associated with adverse outcomes in many diseases. This study aimed to explore the prognostic value of GG on long-term outcomes of spontaneous intracerebral hemorrhage (sICH). METHODS: The current study included 528 patients from a multicenter, prospective, consecutive, observational cohort study. Poor clinical outcome was defined as modified Rankin Scale ≥ 3. GG was calculated using admission blood glucose minus hemoglobin A1c-derived average blood glucose. Logistic regression analyses were performed to determine the association between GG and poor clinical outcomes at 30 days, 90 days, and 1 year. RESULTS: Glycemic gap was significantly associated with poor clinical outcomes at 30 days, 90 days, and 1 year (p < 0.05 for all models), where patients with higher GG were more likely to have poor clinical outcome. Restricted cubic splines revealed a positive association between GG and poor clinical outcome. In addition, patients with higher GG were more likely to have a higher 1-year mortality rate. The addition of GG to the intracerebral hemorrhage score improved the discrimination and calibration properties for the prediction of poor clinical outcome. CONCLUSIONS: Glycemic gap was independently associated with poor outcomes and may be a valuable prognostic factor in patients with sICH.

Prior statin and short-term outcomes of primary intracerebral hemorrhage: From a large-scale nationwide longitudinal registry.

INTRODUCTION: The relationship between statins and intracerebral hemorrhage outcomes is unclear. AIM: We aimed to compare the in-hospital mortality and evacuation of intracranial hematoma rates in patients with primary intracerebral hemorrhage between prior statin users and nonusers. RESULTS: The final study population included 66,263 patients. Multivariable logistics analyses showed that prior statin use was not associated with in-hospital mortality for primary intracerebral hemorrhage (adjusted odd ratio 0.78, 95% CI 0.61-1.01), but reduced the proportion of patients undergoing evacuation of intracranial hematoma (adjusted odd ratio 0.70, 95% CI 0.61-0.82). Propensity score matching analyses yielded similar results. CONCLUSION: Prior statin use was not associated with in-hospital mortality but did reduce evacuation of intracranial hematoma rates.

Tenecteplase in Ischemic Stroke: Challenge and Opportunity.

Purpose of Review: Intravenous thrombolysis is the first-line therapy for ischemic stroke, and alteplase has been used as an intravenous thrombolysis drug for over 20 years. However, considering its low rate of recanalization and risk of intracerebral hemorrhage, alteplase may not be the optimal thrombolytic drug of choice for ischemic stroke. Tenecteplase (TNK) is a genetically engineered, mutant, tissue plasminogen activator that is a potential substitute to alteplase in ischemic stroke. The pharmacokinetic advantages of TNK include greater fibrin selectivity than alteplase and prolonged half-life time. In this review, we have summarized the clinical trials of TNK in ischemic stroke. Recent Findings: Clinical trials showed a higher recanalization rate of TNK over alteplase without increasing the rate of intracerebral hemorrhage. However, not all clinical trials showed superiority of TNK over alteplase in functional outcomes and early neurological improvement. TNK was superior to alteplase in terms of recanalization in patients who fulfilled the imaging mismatch criteria and in those planning to undergo mechanical thrombectomy. Summary: TNK has the potential to substitute alteplase for ischemic stroke therapy. Future TNK clinical trials that target functional outcomes are warranted.

Isolation, characterization, and genome assembly of Barnettozyma botsteinii sp. nov. and novel strains of Kurtzmaniella quercitrusa isolated from the intestinal tract of the termite Macrotermes bellicosus.

Bioconversion of hemicelluloses into simpler sugars leads to the production of a significant amount of pentose sugars, such as d-xylose. However, efficient utilization of pentoses by conventional yeast production strains remains challenging. Wild yeast strains can provide new industrially relevant characteristics and efficiently utilize pentose sugars. To explore this strategy, we isolated gut-residing yeasts from the termite Macrotermes bellicosus collected in Comoé National Park, Côte d'Ivoire. The yeasts were classified through their Internal Transcribed Spacer/Large Subunit sequence, and their genomes were sequenced and annotated. We identified a novel yeast species, which we name Barnettozyma botsteinii sp. nov. 1118T (MycoBank: 833563, CBS 16679T and IBT 710) and two new strains of Kurtzmaniella quercitrusa: var. comoensis (CBS 16678, IBT 709) and var. filamentosus (CBS 16680, IBT 711). The two K. quercitrusa strains grow 15% faster on synthetic glucose medium than Saccharomyces cerevisiae CEN.PKT in acidic conditions (pH = 3.2) and both strains grow on d-xylose as the sole carbon source at a rate of 0.35 h-1. At neutral pH, the yeast form of K. quercitrusa var. filamentosus, but not var. comoensis, switched to filamentous growth in a carbon source-dependent manner. Their genomes are 11.0-13.2 Mb in size and contain between 4888 and 5475 predicted genes. Together with closely related species, we did not find any relationship between gene content and ability to grow on xylose. Besides its metabolism, K. quercitrusa var. filamentosus has a large potential as a production organism, because of its capacity to grow at low pH and to undergo a dimorphic shift.

Leptosphaerulina species isolated from golf turfgrass in China, with description of L. macrospora, sp. nov.

Leptosphaerulina leaf blight occurs on most turfgrasses. Hitherto, Leptosphaerulina species associated with this disease include L. americana, L. argentinensis, L. australis, and L. trifolii. However, following Koch's postulates, L. australis was confirmed as saprobes but not pathogens, and the other three species have not been tested. The pathogenicity of Leptosphaerulina spp. is still questionable. In this study, we isolated 19 Leptosphaerulina strains from diseased golf turfgrasses in China, and they were identified as L. gaeumannii, L. saccharicola, and a new species, L. macrospora, through multilocus (ITS, 28S, rpb2, and tub2) phylogenetic analyses and morphological observations. Pathogenicity test revealed that the three Leptosphaerulina species identified in this study cannot infect live/healthy turfgrass tissues of Poa pratensis and Agrostis stolonifera and only produced pseudothecia on the dead leaves of stressed seedlings. Considering the results of pathogenicity tests in this and previous studies, we speculate that most Leptosphaerulina species isolated from diseased turfgrass are not pathogens but saprobes. Applying proper management practices to prevent severe turfgrass stress is a key measure to reduce or eliminate the effects of Leptosphaerulina on golf turfgrass.