Association of blood pressure and outcomes differs upon cerebral perfusion post-thrombectomy in patients with acute ischemic stroke.

BACKGROUND: The relationship between post-endovascular thrombectomy (EVT) blood pressure (BP) and outcomes in patients with acute ischemic stroke (AIS) remains contentious. We aimed to explore whether this association differs with different cerebral perfusion statuses post-EVT. METHODS: In a multicenter observational study of patients with AIS with large vessel occlusion who underwent EVT, we enrolled those who accepted CT perfusion (CTP) imaging within 24 hours post-EVT. We recorded post-EVT systolic (SBP) and diastolic BP. Patients were stratified into favorable perfusion and unfavorable perfusion groups based on the hypoperfusion intensity ratio (HIR) on CTP. The primary outcome was good functional outcome (90-day modified Rankin Scale score of ≤3). Secondary outcomes included early neurological deterioration, infarct size growth, and symptomatic intracranial hemorrhage. RESULTS: Of the 415 patients studied (mean age 62 years, 75% male), 233 (56%) achieved good functional outcomes. Logistic regression showed that post-EVT HIR and 24-hour mean SBP were significantly associated with functional outcomes. Among the 326 (79%) patients with favorable perfusion, SBP <140 mmHg was associated with a higher percentage of good functional outcomes compared with SBP ≥140 mmHg (68% vs 52%; aOR 1.70 (95% CI 1.00 to 2.89), P=0.04). However, no significant difference was observed between SBP and functional outcomes in the unfavorable perfusion group. There was also no discernible difference between SBP and secondary outcomes across the different perfusion groups. CONCLUSIONS: In patients with favorable perfusion post-EVT, SBP <140 mmHg was associated with good functional outcomes, which underscores the need for further investigations with larger sample sizes or a more individualized BP management strategy. CLINICAL TRIAL REGISTRATION: ChiCTR1900022154.

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Production of antibodies and antibody fragments containing non-natural amino acids in Escherichia coli.

Therapeutic bioconjugates are emerging as an essential tool to combat human disease. Site-specific conjugation technologies are widely recognized as the optimal approach for producing homogeneous drug products. Non-natural amino acid (nnAA) incorporation allows the introduction of bioconjugation handles at genetically defined locations. Escherichia coli (E. coli) is a facile host for therapeutic nnAA protein synthesis because it can stably replicate plasmids encoding genes for product and nnAA incorporation. Here, we demonstrate that by engineering E. coli to incorporate high levels of nnAAs, it is feasible to produce nnAA-containing antibody fragments and full-length immunoglobulin Gs (IgGs) in the cytoplasm of E. coli. Using high-density fermentation, it was possible to produce both of these types of molecules with site-specifically incorporated nnAAs at titers > 1 g/L. We anticipate this strategy will help simplify the production and manufacture of promising antibody therapeutics.

Prediction of futile recanalisation after endovascular treatment in acute ischaemic stroke: development and validation of a hybrid machine learning model.

BACKGROUND: Identification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid machine learning method for predicting futile recanalisation. METHODS: Hybrid machine learning models were developed to address six clinical scenarios within the EVT and perioperative management workflow. These models were trained on a prospective database using hybrid feature selection technique to predict futile recanalisation following EVT. The optimal model was validated and compared with existing models and scoring systems in a multicentre prospective cohort to develop a hybrid machine learning-based risk stratification system for futile recanalisation prediction. RESULTS: Using a hybrid feature selection approach, we trained and tested multiple classifiers on two independent patient cohorts (n=1122) to develop a hybrid machine learning-based prediction model. The model demonstrated superior discriminative ability compared with other models and scoring systems (area under the curve=0.80, 95% CI 0.73 to 0.87) and was transformed into a web application (RESCUE-FR Index) that provides a risk stratification system for individual prediction (accessible online at fr-index.biomind.cn/RESCUE-FR/). CONCLUSIONS: The proposed hybrid machine learning approach could be used as an individualised risk prediction model to facilitate adherence to clinical practice guidelines and shared decision-making for optimal candidate selection and prognosis assessment in patients undergoing EVT.

Responses of soil dissolved organic carbon properties to the desertification of desert wetlands in the Mu Us Sandy Land.

In desert wetlands, the decline in ground water table results in desertification, triggering soil carbon and nutrient loss. However, the impacts of desertification on soil dissolved organic carbon (DOC) properties which determine the turnover of soil carbon and nutrients are unclear. Here, the desertification gradient was represented by the distance from the wetland center (0∼240 m) traversing reed marshes, desert shrubs and bare sandy land in the Hongjian Nur Basin, north China. Soil DOC properties were determined by ultraviolet and fluorescence spectroscopy coupled with parallel factor analysis (PARAFAC). Results showed that soil DOC content decreased significantly from 107.23 mg kg-1 to 8.44 mg kg-1 by desertification (p < 0.05). However, the proportion of DOC to soil organic carbon (SOC) was gradually significantly increased. According to spectral parameters, microbial-derived DOC decreased from 0 to 120 m (reed marshes to desert shrubs) but increased from 120 to 240 m (desert shrubs to bare sandy lands), with a reverse hump-shaped distribution pattern. The molecular weight and aromaticity of DOC increased from 0 to 120 m but decreased from 120 to 240 m, with a hump-shaped distribution pattern. For the DOC composition, although the relative abundances of humic-acid components remained stable (p > 0.05), they were ultimately decreased by serious desertification and the amino acids became the dominant component. A similar change pattern was also found for humification index. Additionally, MBC and C:N were the two most important variables in determining the content and spectral properties, respectively. Together, these findings relationships between the soil DOC properties and desertification degree, especially the increase in DOC proportion and the decrease in humification degree, which may reduce soil C stabilization in the Hongjian Nur Basin.

Binding characteristics of pheromone-binding protein 1 in Glyphodes pyloalis to organophosphorus insecticides: Insights from computational and experimental approaches.

Glyphodes pyloalis (Lepidoptera: Pyralidae) is one of the major pests in mulberry production in China, which has developed resistance to various insecticides. Chemoreception is one of the most crucial physiological tactics in insects, playing a pivotal role in recognizing chemical stimuli in the environment, including noxious stimuli such as insecticides. Herein, we obtained recombinant pheromone-binding protein 1 (GpylPBP1) that exhibited antennae-biased expression in G. pyloalis. Ligand-binding assays indicated that GpylPBP1 had the binding affinities to two organophosphorus insecticides, with a higher binding affinity to chlorpyrifos than to phoxim. Computational simulations showed that a mass of nonpolar amino acid residues formed the binding pocket of GpylPBP1 and contributed to the hydrophobic interactions in the bindings of GpylPBP1 to both insecticides. Furthermore, the binding affinities of three GpylPBP1 mutants (F12A, I52A, and F118A) to both insecticides were all significantly reduced compared to those of the GpylPBP1-wild type, suggesting that Phe12, Ile52, and Phe118 residues were crucial binding sites and played crucial roles in the bindings of GpylPBP1 to both insecticides. Our findings can be instrumental in elucidating the effects of insecticides on olfactory recognition in moths and facilitating the development of novel pest management strategies using PBPs as targets based on insect olfaction.

Cp*Rh(III)-catalyzed regioselective cyclization of aromatic amides with allenes.

A new Cp*Rh(III)-catalyzed regioselective cyclization reaction of aromatic amides with allenes is reported. The use of allenyl derivatives bearing a directing-group assistant as a reaction promoter was the key to the success of this protocol. In this catalytic system, N-(pivaloyloxy)benzamide substrates react with allenes via Rh-σ-alkenyl intermediates, while N-(pivaloyloxy) indol substrates react via Rh-π-allyl intermediates. These reactions were characterized by mild reaction conditions, a broad substrate scope, and high functional-group compatibility to yield several high-value isoquinolinone and pyrimido[1,6-a]indol-1(2H)-one skeleton-containing compounds. The synthetic applications and primary mechanisms were also investigated.

A cellular platform for production of C4 monomers.

Living organisms carry out a wide range of remarkable functions, including the synthesis of thousands of simple and complex chemical structures for cellular growth and maintenance. The manipulation of this reaction network has allowed for the genetic engineering of cells for targeted chemical synthesis, but it remains challenging to alter the program underlying their fundamental chemical behavior. By taking advantage of the unique ability of living systems to use evolution to find solutions to complex problems, we have achieved yields of up to ∼95% for three C4 commodity chemicals, n-butanol, 1,3-butanediol, and 4-hydroxy-2-butanone. Genomic sequencing of the evolved strains identified pcnB and rpoBC as two gene loci that are able to alter carbon flow by remodeling the transcriptional landscape of the cell, highlighting the potential of synthetic pathways as a tool to identify metabolic control points.

Diagnostic accuracy of left atrial function and strain for differentiating between acute and chronic myocardial infarction.

BACKGROUND: The cardiac magnetic resonance tissue tracking (CMR-TT) technique was used to obtain left atrial strain and strain rate in patients with myocardial infarction (MI) and to evaluate the utility of this technique in the quantitative assessment of myocardial infarction for distinguishing acute from chronic myocardial infarction. METHODS: We retrospectively analyzed 36 consecutive patients with acute myocardial infarction (AMI) and 29 patients with chronic myocardial infarction (CMI) who underwent CMR and 30 controls. Left atrial (LA) and ventricular functions were quantified by volumetric, and CMR-TT derived strain analysis from long and short left ventricular view cines. Receiver Operating Characteristics (ROC) analysis was used to determine the diagnostic accuracy of CMR-TT strain parameters for discriminating between acute and chronic myocardial infarction. RESULTS: AMI and CMI participants had impaired LA reservoir function, conduit function and LA booster pump dysfunction compared to the controls. LA strain was more sensitive than LV global strain for the assessment of the MI stage. Peak late-negative SR yielded the best areas under the ROC curve (AUC) of 0.879, showing differentiation between acute and chronic myocardial infarction of all the LA strain parameters obtained. The highest significant differences between chronic myocardial infarction and normal myocardium were also found in the LV strain (p < 0.001) and LA functional parameters (p < 0.001), but there was no difference between AMI and normals. CONCLUSIONS: CMR-TT-derived LA strain is a potential and robust tool in demonstrating impaired LA mechanics and quantifying LA dynamics, which have high sensitivity and specificity in the differential diagnosis of acute versus chronic myocardial infarction. Their use is thus worth popularizing in clinical application.

Insights into the mechanisms of triptolide nephrotoxicity through network pharmacology-based analysis and RNA-seq.

Introduction: Triptolide (TPL) is a promising plant-derived compound for clinical therapy of multiple human diseases; however, its application was limited considering its toxicity. Methods: To explore the underlying molecular mechanism of TPL nephrotoxicity, a network pharmacology based approach was utilized to predict candidate targets related with TPL toxicity, followed by deep RNA-seq analysis to characterize the features of three transcriptional elements include protein coding genes (PCGs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) as well as their associations with nephrotoxicity in rats with TPL treatment. Results & Discussion: Although the deeper mechanisms of TPL nephrotoxcity remain further exploration, our results suggested that c-Jun is a potential target of TPL and Per1 related circadian rhythm signaling is involved in TPL induced renal toxicity.

Comparison of four screening methods for sarcopenia among community-dwelling older adults: A diagnostic accuracy study.

This study aimed to compare the diagnostic values of SARC-F (strength, assistance with walking, rising from a chair, climbing stairs, and falls), SARC-Calf (SARC-F combined with calf circumference), CC (calf circumference), and the Yubi-wakka (finger-ring) test for screening for sarcopenia in community-dwelling older adults. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used as a standard reference. A total of 209 participants were enrolled, and 40.7% were identified as sarcopenia. The sensitivity, specificity, and AUC were respectively 54.1%, 70.2%, and 0.687 for SARC-F; 76.5%, 73.4% and 0.832 for SARC-calf, 86.7%, 82.4%, and 0.906 for CC in men, and 85.5%, 63.3%, and 0.877 for CC in women. Relative to the "bigger," a significant association between sarcopenia and the Yubi-wakka test ("just fits" OR: 4.1, 95% CI: 1.57-10.98; "small" OR: 27.5, 95% CI: 10.14-74.55) was observed. The overall accuracy of CC was better than SARC-Calf for sarcopenia screening.

Increased serum uric acid level is associated with better outcome after endovascular treatment for acute ischemic stroke-a prospective cohort study.

Background: The role of serum uric acid (SUA) in affecting outcomes after endovascular treatment (EVT) in patients with ischemic stroke remains unclear. This study investigated the association of SUA with outcomes of patients with acute large vessel occlusion (LVO) who had received EVT. Methods: Patients with acute LVO stroke who underwent EVT within 24 hours were enrolled from a prospective, nationwide registry study. Baseline characteristics and SUA level within 24 hours of EVT were collected. The primary outcome was an excellent 90-day functional outcome [modified Rankin Scale (mRS) score 0-1]. Secondary outcomes included a favorable 90-day outcome (mRS score 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. The SUA level was analyzed in quartiles and as a continuous variable. We investigated the independent association of SUA with the primary outcome using multivariable logistic regression. Results: Among 780 patients (mean age 64 years; 66.28% males), 230 (29.49%) had an excellent 90-day outcome. A higher SUA level was significantly associated with an excellent outcome in univariate logistic regression (P=0.045) and after adjusting for confounders in multivariate analysis [adjusted odds ratio (aOR), 0.998; 95% confidence interval (CI), 0.996-1.000; P=0.018]. Multivariate logistic regression analysis showed patients with SUA level in the fourth quartile had an excellent 90-day outcome (aOR, 0.367; 95% CI, 0.154-0.876; P=0.024). There was no significant association for SUA level with favorable 90-day outcome, sICH, or 90-day mortality (P>0.05). Conclusions: Among patients with acute LVO type of stroke who received EVT, baseline high SUA level may predict a better 90-day functional outcome.

Small vessel disease burden may not portend unfavorable outcome after thrombectomy for acute large vessel occlusion.

OBJECTIVES: We aimed to investigate the correlation between an overall cerebral small vessel disease (CSVD) burden and outcomes after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: In a multicenter registry study, we enrolled patients with EVT for anterior-circulation LVO-stroke. In 3.0-T MR imaging, we assessed 4 CSVD imaging markers, lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces, each assigned a score of 0 or 1 and summed up to an overall CSVD burden score of 0-4. We dichotomized the overall CSVD severity as none to mild (score 0-2) and moderate to severe (3-4). Primary outcome was 90-day functional dependence or death (modified Rankin Scale (mRS) 3-6). Secondary outcomes included increase in NIH Stroke Scale ≥ 4 within 24 h (early neurological deterioration (END)) and within 7 days, symptomatic intracranial hemorrhage, 90-day mRS 2-6, and 90-day mortality. RESULTS: Among 311 patients (63.0% male; mean age 65.1 ± 12.7 years), 260 (83.6%) had none-to-mild and 51 (16.4%) had moderate-to-severe overall CSVD burden. Moderate-to-severe CSVD burden was not significantly associated with the primary outcome (47.1% versus 45.4%; p > 0.05 in univariate and multivariate logistic regression), or the secondary outcomes except for a higher risk of END (11.8% versus 3.1%; p < 0.05 in multivariate analyses). Sensitivity analyses with 0-1 versus 2-4 of the CSVD burden score, and the score as an ordinal variable, showed similar results. CONCLUSIONS: An overall moderate-to-severe CSVD burden was not associated with 90-day functional dependence or death, after EVT for anterior-circulation LVO. TRIAL REGISTRATION: ChiCTR1900022154 KEY POINTS: • Moderate-to-severe cerebral small vessel disease burden on MRI should not be an exclusion indicator in determining the eligibility of an acute ischemic stroke patient for endovascular treatment.

Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion.

BACKGROUND AND PURPOSE: It remains controversial if endovascular treatment (EVT) can improve the outcome of patients with acute basilar artery occlusion (BAO). This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis (IVT) first in patients who had acute ischaemic stroke (AIS) due to BAO. METHODS: Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study, and the efficacy and safety were compared between IVT+EVT and direct EVT. The primary outcome was 90-day functional independence. All outcomes were assessed with adjusted OR (aOR) from the multivariable logistic regression. In addition, a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO. RESULTS: Of 310 enrolled patients with BAO, 241 (78%) were treated with direct EVT and 69 (22%) with IVT+EVT. Direct EVT was associated with a worse functional outcome (aOR, 0.46 (95% CI 0.24 to 0.85), p=0.01). IVT+EVT was associated with a lower percentage of patients who needed ≥3 passes of stent retriever (10.14% vs 20.75%). The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence (r=0.14 (95% CI 0.05 to 0.24), p<0.01). CONCLUSIONS: This study showed that compared with direct EVT, EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset. The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.

Comparison of clinical characteristics in patients with coronavirus disease and influenza A in Guangzhou, China.

BACKGROUND: This study aims to compare the epidemiological, clinical and laboratory characteristics between patients with coronavirus disease (COVID-19) and influenza A (H1N1), and to develop a differentiating model and a simple scoring system. METHODS: We retrospectively analyzed the data from patients with COVID-19 and H1N1. The logistic regression model based on clinical and laboratory characteristics was constructed to distinguish COVID-19 from H1N1. Scores were assigned to each of independent discrimination factors based on their odds ratios. The performance of the prediction model and scoring system was assessed. RESULTS: A total of 236 patients were recruited, including 20 COVID-19 patients and 216 H1N1 patients. Logistic regression revealed that age >34 years, temperature ≤37.5 °C, no sputum or myalgia, lymphocyte ratio ≥20% and creatine kinase-myocardial band isoenzyme (CK-MB) >9.7 U/L were independent differentiating factors for COVID-19. The area under curves (AUCs) of the prediction model and scoring system in differentiating COVID-19 from H1N1 were 0.988 and 0.962, respectively. CONCLUSIONS: There are certain differences in clinical and laboratory features between patients with COVID-19 and H1N1. The simple scoring system may be a useful tool for the early identification of COVID-19 patients from H1N1 patients.

Funneliformis mosseae Improves Growth and Nutrient Accumulation in Wheat by Facilitating Soil Nutrient Uptake under Elevated CO2 at Daytime, Not Nighttime.

The concurrent effect of elevated CO2 (eCO2) concentrations and arbuscular mycorrhizal fungi (AMF) on plant growth, carbon (C), nitrogen (N), phosphorus (P) and potassium (K) accumulations in plant and soil is largely unknown. To understand the mechanisms of eCO2 and mycorrhization on wheat (Triticum aestivum) performance and soil fertility, wheat seedlings were grown under four different CO2 environments for 12 weeks, including (1) ambient CO2 (ACO2, 410/460 ppm, daytime/nighttime), (2) sole daytime eCO2 (DeCO2, 550/460 ppm), (3) sole nighttime eCO2 (NeCO2, 410/610 ppm), and (4) dual or continuous daytime/nighttime eCO2 ((D + N)eCO2, 550/610 ppm), and with or without AMF (Funneliformis mosseae) colonization. DeCO2, NeCO2 and (D + N)eCO2 generally significantly increased shoot and root biomass, plant C, N, P and K accumulation, soil invertase and urease activity, but decreased shoot and root N, P and K concentrations, and soil available N, P and K. Compared with non-AMF, AMF effects on above-mentioned characteristics were significantly positive under ACO2, DeCO2 and (D + N)eCO2, but negative on plant biomass, C, N, P and K accumulation under NeCO2. Overall, AMF colonization alleviated soil nutrient constraints on plant responses to DeCO2, while NeCO2 decreased AMF's beneficial effects on plants. These results demonstrated that an integration of AMF's benefits to plants under factual field DeCO2 and/or NeCO2 will be critical for managing the long-term consequence of future CO2 rising on global cropping systems.

Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Studies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion. METHODS: We did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Of the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency. CONCLUSIONS: Among patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

Haemostatic therapy in spontaneous intracerebral haemorrhage patients with high-risk of haematoma expansion by CT marker: a systematic review and meta-analysis of randomised trials.

BACKGROUND AND PURPOSE: Current randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs. METHODS: A comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality. RESULTS: The meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death. CONCLUSIONS: Haemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.