The overview of the BioRED (Biomedical Relation Extraction Dataset) track at BioCreative VIII.

The BioRED track at BioCreative VIII calls for a community effort to identify, semantically categorize, and highlight the novelty factor of the relationships between biomedical entities in unstructured text. Relation extraction is crucial for many biomedical natural language processing (NLP) applications, from drug discovery to custom medical solutions. The BioRED track simulates a real-world application of biomedical relationship extraction, and as such, considers multiple biomedical entity types, normalized to their specific corresponding database identifiers, as well as defines relationships between them in the documents. The challenge consisted of two subtasks: (i) in Subtask 1, participants were given the article text and human expert annotated entities, and were asked to extract the relation pairs, identify their semantic type and the novelty factor, and (ii) in Subtask 2, participants were given only the article text, and were asked to build an end-to-end system that could identify and categorize the relationships and their novelty. We received a total of 94 submissions from 14 teams worldwide. The highest F-score performances achieved for the Subtask 1 were: 77.17% for relation pair identification, 58.95% for relation type identification, 59.22% for novelty identification, and 44.55% when evaluating all of the above aspects of the comprehensive relation extraction. The highest F-score performances achieved for the Subtask 2 were: 55.84% for relation pair, 43.03% for relation type, 42.74% for novelty, and 32.75% for comprehensive relation extraction. The entire BioRED track dataset and other challenge materials are available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/ and https://codalab.lisn.upsaclay.fr/competitions/13377 and https://codalab.lisn.upsaclay.fr/competitions/13378. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/https://codalab.lisn.upsaclay.fr/competitions/13377https://codalab.lisn.upsaclay.fr/competitions/13378.

Circulating platelets modulate oligodendrocyte progenitor cell differentiation during remyelination.

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.

De novo anaerobic granulation with varying organic substrates: granule growth and microbial community responses.

Anaerobic granulation from dispersed inoculum is recognized as a slow process. However, studies under saline conditions have shown that adding complex proteinaceous substrates can accelerate this process. To explore whether this holds true also under non-saline conditions, we conducted a 262-days experiment with four lab-scale upflow anaerobic sludge blanket reactors inoculated with digested sewage sludge. Each reactor received a synthetic feed containing varying amount of carbohydrate/protein substrate: glucose (RGlu), acetate/tryptone (RAc+Try), glucose/tryptone (RGlu+Try), and glucose/starch (RGlu+Sta). Development of granules with different influent composition was monitored with macroscopy, analysis of the extracellular polymeric substances, and microbial diversity. Granulation was faster in reactors RGlu+Try and RGlu+Sta. Increasing granule diameters positively correlated with the occurrence of bacteria from Muribaculaceae and Lachnospiraceae families, suggesting their involvement in de novo granulation. Granules of RGlu+Try also had high relative abundances of both fermenting bacteria (e.g. Lactococcus, Streptococcus, Trichococcus) and bacteria involved in the oxidation of volatile fatty acids (Smithella, Acetobacteroides). The results of this study provide a basis for strategies to enhance the sludge granulation rate in practice when granular inoculum is not available. Specifically, supplementing small amounts of waste protein during reactor start-up can be effective.

Basilar artery occlusion management: An international survey of gender influence on management.

BACKGROUND: The superiority of endovascular thrombectomy (EVT) over medical management was not established in two early basilar artery occlusion (BAO) randomized controlled trials. Despite this, many clinicians recommended EVT for acute BAO under certain circumstances. This paper aims to compare physicians' diagnostic and management strategies of BAO according to gender. METHODS: From January to March 2022 an international survey was conducted regarding management strategies in acute BAO. We compared responses between clinicians by identifying gender. Questions were designed to examine clinical and imaging parameters influencing management of patients with BAO. RESULTS: Among the 1245 respondents from 73 countries, 311 (25.0%) identified as female. This figure was 13.6% amongst interventionists. Geographically, female respondents were lowest in Asia (14.5%) and North America (23.9%). The proportion of respondents identifying as female was consistent regardless of their years of experience. Female respondents were more likely to choose time of onset as time of first estimated stroke like symptom (48.0% vs. 38.5%, p < .01), were less likely to favor thrombectomy in the V4 segment of vertebrobasilar artery occlusions (31.5% vs. 43.3%, p < .01), and were less likely to find it acceptable to enroll all patients who met trial criteria in the standard medical treatment arm of a clinical trial (41.2% vs. 47.0%, p = .01). Male respondents were more likely to agree that thrombolysis would not alter their decision on proceeding with EVT (93.7% vs. 88.3%, p < .01). CONCLUSIONS: Female clinicians appear to be significantly underrepresented in stroke medicine. This is most pronounced amongst interventionists and in Asia. Although male and female opinions were closely aligned on many aspects of BAO management, differences in opinion were observed in a number of significant areas which influence decision making.

Mechanisms of microbial co-aggregation in mixed anaerobic cultures.

Co-aggregation of anaerobic microorganisms into suspended microbial biofilms (aggregates) serves ecological and biotechnological functions. Tightly packed aggregates of metabolically interdependent bacteria and archaea play key roles in cycling of carbon and nitrogen. Additionally, in biotechnological applications, such as wastewater treatment, microbial aggregates provide a complete metabolic network to convert complex organic material. Currently, experimental data explaining the mechanisms behind microbial co-aggregation in anoxic environments is scarce and scattered across the literature. To what extent does this process resemble co-aggregation in aerobic environments? Does the limited availability of terminal electron acceptors drive mutualistic microbial relationships, contrary to the commensal relationships observed in oxygen-rich environments? And do co-aggregating bacteria and archaea, which depend on each other to harvest the bare minimum Gibbs energy from energy-poor substrates, use similar cellular mechanisms as those used by pathogenic bacteria that form biofilms? Here, we provide an overview of the current understanding of why and how mixed anaerobic microbial communities co-aggregate and discuss potential future scientific advancements that could improve the study of anaerobic suspended aggregates. KEY POINTS: • Metabolic dependency promotes aggregation of anaerobic bacteria and archaea • Flagella, pili, and adhesins play a role in the formation of anaerobic aggregates • Cyclic di-GMP/AMP signaling may trigger the polysaccharides production in anaerobes.

Adipose tissue-liver cross-talk: a route to hepatic dysfunction in pregnant women with obesity.

Obesity during pregnancy has been escalating, becoming a huge problem that poses consequences not only for the health of the offspring but also for the maternal well-being. Women's adipose and hepatic tissue metabolism undergoes significant changes during the gestational period. During pregnancy, obesity is a primary instigator of steatosis, increasing the risk of non-alcholic fatty liver disease (NAFLD), now recognized under the updated nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). Pregnant women with obesity present higher levels of free fatty acids and glucose, reduction in insulin sensitivity, and adipose tissue endocrine dysregulation. Furthermore, obesity-induced modifications in clock genes and lipid-associated gene expression within adipose tissue disrupt crucial metabolic adaptations, potentially culminating in adipose tissue dysfunction. Thus, the liver experiences increased exposure to free fatty acids through the portal vein. Higher uptake of free fatty acids into the liver disrupts hepatic lipid oxidation while enhances lipogenesis, thereby predisposing to ectopic fat deposition within the liver. This review focuses on the obesity-induced changes during pregnancy in both liver and adipose tissue metabolism, elucidating how the metabolic crosstalk between these two organs can be dysregulated in pregnant women living with obesity.

Isolation of a methyl-reducing methanogen outside the Euryarchaeota.

Methanogenic archaea are main contributors to methane emissions, and have a crucial role in carbon cycling and global warming. Until recently, methanogens were confined to Euryarchaeota, but metagenomic studies revealed the presence of genes encoding the methyl coenzyme M reductase complex in other archaeal clades1-4, thereby opening up the premise that methanogenesis is taxonomically more widespread. Nevertheless, laboratory cultivation of these non-euryarchaeal methanogens was lacking to corroborate their potential methanogenic ability and physiology. Here we report the isolation of a thermophilic archaeon LWZ-6 from an oil field. This archaeon belongs to the class Methanosuratincolia (originally affiliated with 'Candidatus Verstraetearchaeota') in the phylum Thermoproteota. Methanosuratincola petrocarbonis LWZ-6 is a strict hydrogen-dependent methylotrophic methanogen. Although previous metagenomic studies speculated on the fermentative potential of Methanosuratincolia members, strain LWZ-6 does not ferment sugars, peptides or amino acids. Its energy metabolism is linked only to methanogenesis, with methanol and monomethylamine as electron acceptors and hydrogen as an electron donor. Comparative (meta)genome analysis confirmed that hydrogen-dependent methylotrophic methanogenesis is a widespread trait among Methanosuratincolia. Our findings confirm that the diversity of methanogens expands beyond the classical Euryarchaeota and imply the importance of hydrogen-dependent methylotrophic methanogenesis in global methane emissions and carbon cycle.

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial.

BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms. RESULTS: Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was -2.2% (95% CI, -7.8% to 3.5%) in people with HT (HI: -4.7% [95% CI, -10.8% to 1.4%]; PH: 6.1% [95% CI, -8.5% to 20.6%]) and -0.9% (95% CI, -2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3-6) was 11.5% (95% CI, -0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, -6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and -2.6% (95% CI, -7.1% to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown. Objective: To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation. Design, Setting, and Participants: Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis. Intervention: Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke. Main Outcomes and Measures: The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined. Results: A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters. Conclusions and Relevance: The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03148457.

Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis: The BEAST Study.

BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.

A large-scale machine learning analysis of inorganic nanoparticles in preclinical cancer research.

Owing to their distinct physical and chemical properties, inorganic nanoparticles (NPs) have shown promising results in preclinical cancer therapy, but designing and engineering them for effective therapeutic purposes remains a challenge. Although a comprehensive database of inorganic NP research is not currently available, it is crucial for developing effective cancer therapies. In this context, machine learning (ML) has emerged as a transformative tool, but its adaptation to nanomedicine is hindered by inexistent or small datasets. Here we assembled a large database of inorganic NPs, comprising experimental datasets from 745 preclinical studies in cancer nanomedicine. Using descriptive statistics and explainable ML models we mined this database to gain knowledge of inorganic NP design patterns and inform future NP research for cancer treatment. Our analyses suggest that NP shape and therapy type are prominent features in determining in vivo efficacy, measured as a percentage of tumour reduction. Moreover, our database provides a large-scale open-access resource for discriminative ML that the broader nanotechnology community can utilize. Our work blueprints data mining for translational cancer research and offers evidence for standardizing NP reporting to accelerate and de-risk inorganic NP-based drug delivery, which may help to improve patient outcomes in clinical settings.

Nursing interventions to promote dyspnea self-management of complex chronic patients: An integrated review.

Objectives: Chronic dyspnea, a distressing symptom in patients with complex chronic conditions, is linked to higher risks of mortality. This study aimed to identify nursing interventions that could improve self-management for complex chronic patients, thereby enhancing control over chronic dyspnea. The findings intend to guide nursing care strategies that promote self-management among this population. Methods: We searched the databases Medline, Scopus, Web of Science, CINAHL, Cochrane Database of Systematic Reviews (CDSR), and Joanna Briggs Institute (JBI) databases were searched in December 2023. We included adult patients with complex chronic conditions with chronic dyspnoea. The team screened articles collaboratively, using Rayyan software. A qualitative appraisal was performed according to JBI Critical Appraisal Checklist tools. The review protocol is registered under the number CRD42023456021. Results: Our review included 18 studies that explored a variety of interventions for chronic dyspnea. We identified pharmacological interventions (such as oxygen therapy and inhalation treatments) and non-pharmacological approaches (including educational programs, breathing exercises, fluid intake management, body awareness techniques, peer support, emotional intelligence training, and the use of web applications). Those interventions empower patients, improve their ability to fulfill life roles, mitigate emotional distress, and improve overall quality of life. Nursing care can be crucial in enabling individuals to achieve independence and autonomy in self-care. Conclusions: Promoting self-management for chronic dyspnea in complex chronic patients requires a holistic approach, encompassing multidisciplinary interventions, individualized self-care education, peer engagement, and technological support. Current research on self-management inadequately addresses interventions targeting patient behaviour change. It highlights the need to delve deeper into the self-management process. Further research is needed to expand the evidence base and refine these interventions.

Transcriptomic evidence for an energetically advantageous relationship between Syntrophomonas wolfei and Methanothrix soehngenii.

Syntrophic interactions are key in anaerobic food chains, facilitating the conversion of complex organic matter into methane. A typical example involves acetogenic bacteria converting fatty acids (e.g., butyrate and propionate), a process thermodynamically reliant on H2 consumption by microorganisms such as methanogens. While most studies focus on H2-interspecies transfer between these groups, knowledge on acetate cross-feeding in anaerobic systems is lacking. This study investigated butyrate oxidation by co-cultures of Syntrophomonas wolfei and Methanospirillum hungatei, both with and without the addition of the acetate scavenger Methanothrix soehngenii. Growth and gene expression patterns of S. wolfei and M. hungatei were followed in the two conditions. Although butyrate consumption rates remained constant, genes in the butyrate degradation pathway of S. wolfei were less expressed in the presence of M. soehngenii, including genes involved in reverse electron transport. Higher expression of a type IV-pili operon in S. wolfei hints to the potential for direct interspecies electron transfer between S. wolfei and M. soehngenii and an energetically advantageous relationship between the two microorganisms. Overall, the presence of the acetate scavenger M. soehngenii positively influenced the energy metabolism of S. wolfei and highlighted the relevance of including acetate scavengers when investigating syntrophic fatty acid degradation.

Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. METHODS: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. RESULTS: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. CONCLUSIONS: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19.

INTRODUCTION: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT. PATIENTS AND METHODS: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex. RESULTS: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02]). CONCLUSION: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls.