Manual Microcatheter-tip Modification: A bailout option for difficult "tip-in" technique during chronic total occlusion percutaneous coronary intervention.

The retrograde approach in chronic total occlusion (CTO) interventions often encounters significant challenges, particularly, when aligning the retrograde microcatheter (MC) with the antegrade system is difficult, complicating or even preventing standard externalization. To address these issues, techniques like the "tip-in" have proven to be effective backup strategies. We introduce the "Manual Microcatheter-tip Modification" (MMM) technique as an alternative when the "tip-in" method faces complications. We present a case of a left anterior descending CTO where MMM was successfully employed for the first time, enabling successful revascularization by manually modifying the MC tip to engage the retrograde guidewire. We explore the technical details within the framework of contemporary CTO PCI. This new technique could enhance the management of CTO interventions, offering innovative solutions when traditional externalization methods are problematic.

Vertical stratification and defensive traits of caterpillars against parasitoids in a lowland tropical forest in Cameroon.

Insect herbivores and their parasitoids play a crucial role in terrestrial trophic interactions in tropical forests. These interactions occur across the entire vertical gradient of the forest. This study compares how caterpillar communities, and their parasitism rates, vary across vertical strata and between caterpillar defensive strategies in a semi deciduous tropical forest in Nditam, Cameroon. Within a 0.1 ha plot, all trees with a diameter at breast height (DBH) ≥ 5 cm were felled and systematically searched for caterpillars. We divided the entire vertical gradient of the forest into eight, five-metre strata. All caterpillars were assigned to a stratum based on their collection height, reared, identified, and classified into one of three defensive traits: aposematic, cryptic and shelter-building. Caterpillar species richness and diversity showed a midstory peak, whereas density followed the opposite pattern, decreasing in the midstory and then increasing towards the highest strata. This trend was driven by some highly dense shelter-building caterpillars in the upper canopy. Specialisation indices indicated decreasing levels of caterpillar generality with increasing height, a midstory peak in vulnerability, and increasing connectance towards the upper canopy, although the latter was likely driven by decreasing network size. Both aposematic and shelter-building caterpillars had significantly higher parasitism rates than cryptic caterpillars. Our results highlight nuanced changes in caterpillar communities across forest strata and provide evidence that defences strategies are important indicators of parasitism rates in caterpillars and that both aposematic and shelter-building caterpillars could be considered a "safe haven" for parasitoids.

Language and ethnobiological skills decline precipitously in Papua New Guinea, the world's most linguistically diverse nation.

Papua New Guinea is home to >10% of the world's languages and rich and varied biocultural knowledge, but the future of this diversity remains unclear. We measured language skills of 6,190 students speaking 392 languages (5.5% of the global total) and modeled their future trends using individual-level variables characterizing family language use, socioeconomic conditions, students' skills, and language traits. This approach showed that only 58% of the students, compared to 91% of their parents, were fluent in indigenous languages, while the trends in key drivers of language skills (language use at home, proportion of mixed-language families, urbanization, students' traditional skills) predicted accelerating decline of fluency to an estimated 26% in the next generation of students. Ethnobiological knowledge declined in close parallel with language skills. Varied medicinal plant uses known to the students speaking indigenous languages are replaced by a few, mostly nonnative species for the students speaking English or Tok Pisin, the national lingua franca. Most (88%) students want to teach indigenous language to their children. While crucial for keeping languages alive, this intention faces powerful external pressures as key factors (education, cash economy, road networks, and urbanization) associated with language attrition are valued in contemporary society.

Impact of Wood Age on Termite Microbial Assemblages.

The decomposition of wood and detritus is challenging to most macroscopic organisms due to the recalcitrant nature of lignocellulose. Moreover, woody plants often protect themselves by synthesizing toxic or nocent compounds which infuse their tissues. Termites are essential wood decomposers in warmer terrestrial ecosystems and, as such, they have to cope with high concentrations of plant toxins in wood. In this paper, we evaluated the influence of wood age on the gut microbial (bacterial and fungal) communities associated with the termites Reticulitermes flavipes (Rhinotermitidae) (Kollar, 1837) and Microcerotermes biroi (Termitidae) (Desneux, 1905). We confirmed that the secondary metabolite concentration decreased with wood age. We identified a core microbial consortium maintained in the gut of R. flavipes and M. biroi and found that its diversity and composition were not altered by the wood age. Therefore, the concentration of secondary metabolites had no effect on the termite gut microbiome. We also found that both termite feeding activities and wood age affect the wood microbiome. Whether the increasing relative abundance of microbes with termite activities is beneficial to the termites is unknown and remains to be investigated. IMPORTANCE Termites can feed on wood thanks to their association with their gut microbes. However, the current understanding of termites as holobiont is limited. To our knowledge, no studies comprehensively reveal the influence of wood age on the termite-associated microbial assemblage. The wood of many tree species contains high concentrations of plant toxins that can vary with their age and may influence microbes. Here, we studied the impact of Norway spruce wood of varying ages and terpene concentrations on the microbial communities associated with the termites Reticulitermes flavipes (Rhinotermitidae) and Microcerotermes biroi (Termitidae). We performed a bacterial 16S rRNA and fungal ITS2 metabarcoding study to reveal the microbial communities associated with R. flavipes and M. biroi and their impact on shaping the wood microbiome. We noted that a stable core microbiome in the termites was unaltered by the feeding substrate, while termite activities influenced the wood microbiome, suggesting that plant secondary metabolites have negligible effects on the termite gut microbiome. Hence, our study shed new insights into the termite-associated microbial assemblage under the influence of varying amounts of terpene content in wood and provides a groundwork for future investigations for developing symbiont-mediated termite control measures.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Distribution of biomass dynamics in relation to tree size in forests across the world.

Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.

Climate variability and aridity modulate the role of leaf shelters for arthropods: A global experiment.

Current climate change is disrupting biotic interactions and eroding biodiversity worldwide. However, species sensitive to aridity, high temperatures, and climate variability might find shelter in microclimatic refuges, such as leaf rolls built by arthropods. To explore how the importance of leaf shelters for terrestrial arthropods changes with latitude, elevation, and climate, we conducted a distributed experiment comparing arthropods in leaf rolls versus control leaves across 52 sites along an 11,790 km latitudinal gradient. We then probed the impact of short- versus long-term climatic impacts on roll use, by comparing the relative impact of conditions during the experiment versus average, baseline conditions at the site. Leaf shelters supported larger organisms and higher arthropod biomass and species diversity than non-rolled control leaves. However, the magnitude of the leaf rolls' effect differed between long- and short-term climate conditions, metrics (species richness, biomass, and body size), and trophic groups (predators vs. herbivores). The effect of leaf rolls on predator richness was influenced only by baseline climate, increasing in magnitude in regions experiencing increased long-term aridity, regardless of latitude, elevation, and weather during the experiment. This suggests that shelter use by predators may be innate, and thus, driven by natural selection. In contrast, the effect of leaf rolls on predator biomass and predator body size decreased with increasing temperature, and increased with increasing precipitation, respectively, during the experiment. The magnitude of shelter usage by herbivores increased with the abundance of predators and decreased with increasing temperature during the experiment. Taken together, these results highlight that leaf roll use may have both proximal and ultimate causes. Projected increases in climate variability and aridity are, therefore, likely to increase the importance of biotic refugia in mitigating the effects of climate change on species persistence.

Sex differences in the Norwegian Tenecteplase Trial (NOR-TEST).

BACKGROUND AND PURPOSE: Sex differences in acute ischemic stroke is of increasing interest in the era of precision medicine. We aimed to explore sex disparities in baseline characteristics, management and outcomes in patients treated with intravenous thrombolysis included in the Norwegian Tenecteplase trial (NOR-TEST). METHODS: NOR-TEST was an open-label, randomized, blinded endpoint trial, performed from 2012 to 2016, comparing treatment with tenecteplase to treatment with alteplase within 4.5 h after acute ischemic stroke symptom onset. Sex differences at baseline, treatment and outcomes were compared using multivariable logistic regression models. Heterogeneity in treatment was evaluated by including an interaction term in the model. RESULTS: Of 1100 patients enrolled, 40% were women, and in patients aged >80 years, the proportion of women was greater than men (19% vs. 14%; p = 0.02). Women had a lower burden of cardiovascular risk factors, such as diabetes mellitus (11% vs. 15%; p = 0.05) and a higher mean high-density lipoprotein cholesterol level (1.7 ± 0.6 mmol/L vs. 1.3 ± 0.4 mmol/L; p < 0.001), and a higher proportion of women had never smoked (45% vs. 33%; p < 0.001) compared with men. While there was no sex difference in time from onset of symptoms to admission, door to needle time or in-hospital workup, women were admitted with more severe stroke (National Institutes of Health Stroke Scale [NIHSS] score 6.2 ± 5.6 vs. 5.3 ± 5.1; p = 0.01). Stroke mimic diagnosis was more common in women (21% vs. 15%; p = 0.01). There were no significant sex differences in clinical outcome, measured by the NIHSS, the modified Rankin Scale, intracranial hemorrhage and mortality. CONCLUSION: Women were underrepresented in number in NOR-TEST. The included women had a lower cardiovascular risk factor burden and more severe strokes.

What Goes in Must Come Out? The Metabolic Profile of Plants and Caterpillars, Frass, And Adults of Asota (Erebidae: Aganainae) Feeding on Ficus (Moraceae) in New Guinea.

Insect herbivores have evolved a broad spectrum of adaptations in response to the diversity of chemical defences employed by plants. Here we focus on two species of New Guinean Asota and determine how these specialist moths deal with the leaf alkaloids of their fig (Ficus) hosts. As each focal Asota species is restricted to one of three chemically distinct species of Ficus, we also test whether these specialized interactions lead to similar alkaloid profiles in both Asota species. We reared Asota caterpillars on their respective Ficus hosts in natural conditions and analyzed the alkaloid profiles of leaf, frass, caterpillar, and adult moth samples using UHPLC-MS/MS analyses. We identified 43 alkaloids in our samples. Leaf alkaloids showed various fates. Some were excreted in frass or found in caterpillars and adult moths. We also found two apparently novel indole alkaloids-likely synthesized de novo by the moths or their microbiota-in both caterpillar and adult tissue but not in leaves or frass. Overall, alkaloids unique or largely restricted to insect tissue were shared across moth species despite feeding on different hosts. This indicates that a limited number of plant compounds have a direct ecological function that is conserved among the studied species. Our results provide evidence for the importance of phytochemistry and metabolic strategies in the formation of plant-insect interactions and food webs in general. Furthermore, we provide a new potential example of insects acquiring chemicals for their benefit in an ecologically relevant insect genus.

Sonothrombolysis in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Evidence about the utility of ultrasound-enhanced thrombolysis (sonothrombolysis) in patients with acute ischemic stroke (AIS) is conflicting. We aimed to evaluate the safety and efficacy of sonothrombolysis in patients with AIS with large vessel occlusion, by analyzing individual patient data of available randomized-controlled clinical trials. METHODS: We included all available randomized-controlled clinical trials comparing sonothrombolysis with or without addition of microspheres (treatment group) to intravenous thrombolysis alone (control group) in patients with AIS with large vessel occlusion. The primary outcome measure was the rate of complete recanalization at 1 to 36 hours following intravenous thrombolysis initiation. We present crude odds ratios (ORs) and ORs adjusted for the predefined variables of age, sex, baseline stroke severity, systolic blood pressure, and onset-to-treatment time. RESULTS: We included 7 randomized controlled clinical trials that enrolled 1102 patients with AIS. A total of 138 and 134 confirmed large vessel occlusion patients were randomized to treatment and control groups respectively. Patients randomized to sonothrombolysis had increased odds of complete recanalization compared with patients receiving intravenous thrombolysis alone (40.3% versus 22.4%; OR, 2.17 [95% CI, 1.03-4.54]; adjusted OR, 2.33 [95% CI, 1.02-5.34]). The likelihood of symptomatic intracranial hemorrhage was not significantly different between the 2 groups (7.3% versus 3.7%; OR, 2.03 [95% CI, 0.68-6.11]; adjusted OR, 2.55 [95% CI, 0.76-8.52]). No differences in the likelihood of asymptomatic intracranial hemorrhage, 3-month favorable functional and 3-month functional independence were documented. CONCLUSIONS: Sonothrombolysis was associated with a nearly 2-fold increase in the odds of complete recanalization compared with intravenous thrombolysis alone in patients with AIS with large vessel occlusions. Further study of the safety and efficacy of sonothrombolysis is warranted.

Connecting high-throughput biodiversity inventories: Opportunities for a site-based genomic framework for global integration and synthesis.

High-throughput sequencing (HTS) is increasingly being used for the characterization and monitoring of biodiversity. If applied in a structured way, across broad geographical scales, it offers the potential for a much deeper understanding of global biodiversity through the integration of massive quantities of molecular inventory data generated independently at local, regional and global scales. The universality, reliability and efficiency of HTS data can potentially facilitate the seamless linking of data among species assemblages from different sites, at different hierarchical levels of diversity, for any taxonomic group and regardless of prior taxonomic knowledge. However, collective international efforts are required to optimally exploit the potential of site-based HTS data for global integration and synthesis, efforts that at present are limited to the microbial domain. To contribute to the development of an analogous strategy for the nonmicrobial terrestrial domain, an international symposium entitled "Next Generation Biodiversity Monitoring" was held in November 2019 in Nicosia (Cyprus). The symposium brought together evolutionary geneticists, ecologists and biodiversity scientists involved in diverse regional and global initiatives using HTS as a core tool for biodiversity assessment. In this review, we summarize the consensus that emerged from the 3-day symposium. We converged on the opinion that an effective terrestrial Genomic Observatories network for global biodiversity integration and synthesis should be spatially led and strategically united under the umbrella of the metabarcoding approach. Subsequently, we outline an HTS-based strategy to collectively build an integrative framework for site-based biodiversity data generation.

Spatial scaling of plant and bird diversity from 50 to 10,000 ha in a lowland tropical rainforest.

While there are numerous studies of diversity patterns both within local communities and at regional scales, the intermediate scale of tens to thousands of km2 is often neglected. Here we present detailed local data on plant communities (using 20 × 20 m plots) and bird communities (using point counts) for a 50 ha ForestGEO plot in lowland rainforest at Wanang, Papua New Guinea. We compare these local diversity patterns with those documented in the surrounding 10,000 ha of lowland rainforest. Woody plant species richness was lower within 50 ha (88% of 10,000 ha richness), even when both were surveyed with identical sampling effort. In contrast, bird communities exhibited identical species accumulation patterns at both spatial scales. Similarity in species composition (Chao-Jaccard) remained constant while similarity in dominance structure (Bray-Curtis) decreased with increased distance between samples across the range from < 1 to 13.8 km for both plant and bird communities. The similarity decay was more rapid in plants, but in both cases was slow. The results indicate low to zero beta-diversity at the spatial scale represented here, particularly for birds but also for woody plants. A 50 ha plot provided a highly accurate representation of broader-scale diversity and community composition within 10,000 ha for birds, and a relatively good representation for woody plants. This suggests potential for wider generalization of data from ForestGEO plots which are almost always locally unreplicated, at least for those in lowland tropical forest.

Spatial covariance of herbivorous and predatory guilds of forest canopy arthropods along a latitudinal gradient.

In arthropod community ecology, species richness studies tend to be prioritised over those investigating patterns of abundance. Consequently, the biotic and abiotic drivers of arboreal arthropod abundance are still relatively poorly known. In this cross-continental study, we employ a theoretical framework in order to examine patterns of covariance among herbivorous and predatory arthropod guilds. Leaf-chewing and leaf-mining herbivores, and predatory ants and spiders, were censused on > 1000 trees in nine 0.1 ha forest plots. After controlling for tree size and season, we found no negative pairwise correlations between guild abundances per plot, suggestive of weak signals of both inter-guild competition and top-down regulation of herbivores by predators. Inter-guild interaction strengths did not vary with mean annual temperature, thus opposing the hypothesis that biotic interactions intensify towards the equator. We find evidence for the bottom-up limitation of arthropod abundances via resources and abiotic factors, rather than for competition and predation.

Clinical outcomes and safety profile of Tenecteplase in wake-up stroke.

BACKGROUND: Tenecteplase has probably pharmacological and clinical advantages in the treatment of acute ischemic stroke. There are lacking data about safety and efficacy of tenecteplase in wake-up stroke (WUPS). AIMS: To investigate safety and efficacy of tenecteplase compared to alteplase in WUPS patients included in NOR-TEST. METHODS: WUPS patients in NOR-TEST were included in the study based on DWI-FLAIR mismatch. Included patients randomly assigned (1:1) to receive intravenous tenecteplase 0.4 mg/kg (to a maximum of 40 mg) or alteplase 0.9 mg/kg (to a maximum of 90 mg). Neurological improvement was defined as 1) favorable functional outcome at 90 days modified Rankin Scale (mRS) of 0 or 1 and 2) neurological improvement measured with the National Institutes of Health Stroke Scale (NIHSS) of 4 points within 24 hours as compared to admission NIHSS or NIHSS 0 at 24 hours. RESULTS: Of 1100 patients from 13 stroke centers included in NOR-TEST, 45 were WUPS patients. Of these, 5 patients were stroke mimics and excluded. Of the remaining 40 patients (3.6%), 24 were treated with alteplase (60%). There was no difference in the number of patients achieving a good clinical outcome (mRS 0-1) in either treatment group. Patients treated with tenecteplase showed a better early neurological improvement (87.5% vs 54.2%, P = 0.027). No ICH was detected on MRI/CT 24-28 hours after thrombolysis. CONCLUSIONS: In WUPS patients treated in NOR-TEST, there was no difference in clinical outcomes at 90 days and no ICH events or deaths were observed in either alteplase- or tenecteplase-treated patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01949948.

Vertical stratification of a temperate forest caterpillar community in eastern North America.

Vertical niche partitioning might be one of the main driving forces explaining the high diversity of forest ecosystems. However, the forest's vertical dimension has received limited investigation, especially in temperate forests. Thus, our knowledge about how communities are vertically structured remains limited for temperate forest ecosystems. In this study, we investigated the vertical structuring of an arboreal caterpillar community in a temperate deciduous forest of eastern North America. Within a 0.2-ha forest stand, all deciduous trees ≥ 5 cm diameter at breast height (DBH) were felled and systematically searched for caterpillars. Sampled caterpillars were assigned to a specific stratum (i.e. understory, midstory, or canopy) depending on their vertical position and classified into feeding guild as either exposed feeders or shelter builders (i.e. leaf rollers, leaf tiers, webbers). In total, 3892 caterpillars representing 215 species of butterflies and moths were collected and identified. While stratum had no effect on caterpillar density, feeding guild composition changed significantly with shelter-building caterpillars becoming the dominant guild in the canopy. Species richness and diversity were found to be highest in the understory and midstory and declined strongly in the canopy. Family and species composition changed significantly among the strata; understory and canopy showed the lowest similarity. Food web analyses further revealed an increasing network specialization towards the canopy, caused by an increase in specialization of the caterpillar community. In summary, our study revealed a pronounced stratification of a temperate forest caterpillar community, unveiling a distinctly different assemblage of caterpillars dwelling in the canopy stratum.

Compound Specific Trends of Chemical Defences in Ficus Along an Elevational Gradient Reflect a Complex Selective Landscape.

Elevational gradients affect the production of plant secondary metabolites through changes in both biotic and abiotic conditions. Previous studies have suggested both elevational increases and decreases in host-plant chemical defences. We analysed the correlation of alkaloids and polyphenols with elevation in a community of nine Ficus species along a continuously forested elevational gradient in Papua New Guinea. We sampled 204 insect species feeding on the leaves of these hosts and correlated their community structure to the focal compounds. Additionally, we explored species richness of folivorous mammals along the gradient. When we accounted for Ficus species identity, we found a general elevational increase in flavonoids and alkaloids. Elevational trends in non-flavonol polyphenols were less pronounced or showed non-linear correlations with elevation. Polyphenols responded more strongly to changes in temperature and humidity than alkaloids. The abundance of insect herbivores decreased with elevation, while the species richness of folivorous mammals showed an elevational increase. Insect community structure was affected mainly by alkaloid concentration and diversity. Although our results show an elevational increase in several groups of metabolites, the drivers behind these trends likely differ. Flavonoids may provide figs with protection against abiotic stressors. In contrast, alkaloids affect insect herbivores and may provide protection against mammalian herbivores and pathogens. Concurrent analysis of multiple compound groups alongside ecological data is an important approach for understanding the selective landscape that shapes plant defences.

Incidence and Etiologies of Stroke Mimics After Incident Stroke or Transient Ischemic Attack.

Background and Purpose- Stroke mimics (SM) pose a common clinical challenge, but the burden of SM in patients with previous ischemic stroke (IS) or transient ischemic attack is unknown. The objective of this study was to calculate the incidence of SM in IS survivors, compare it with the incidence of recurrent stroke in the same population, and explore the time-dependent patterns of SM etiologies. Methods- This prospective cohort study registered SM events and etiologies among 1872 IS and transient ischemic attack survivors diagnosed with index stroke at Haukeland University Hospital stroke unit from 2007 to 2013 by review of medical records. Cumulative incidences of SM were estimated with a competing risks Cox model and compared with incidence of recurrent stroke in the same population. Results- During 8172 person-years of follow-up, 339 patients had 480 SM events. The cumulative incidence rate of SM during follow-up was 58.7 per 1.000 person-years (95% CI, 53.7-64.2) compared with 34.0 per 1.000 person-years (95% CI, 30.2-38.2) for recurrent stroke in the same time period. The risks of SM and recurrent stroke were highest the first year after index IS or transient ischemic attack. The most frequent SM diagnoses were sequelae of cerebral infarction (19.8%), medical observation, and evaluation for suspected cerebrovascular disease (15.6%) and infections (14.0%). The 2 most frequent and unspecific diagnoses (sequelae of cerebral infarction and medical observation) were clustered in the first months after index stroke. Conclusions- SM after IS or transient ischemic attack are more frequent than recurrent stroke and the risk is especially high in the early period. SMs are multietiological and unspecific diagnoses are most frequent early after index stroke.

Safety and Outcomes of Tenecteplase in Moderate and Severe Ischemic Stroke.

Background and Purpose- Tenecteplase represents a promising alternative to alteplase as thrombolytic treatment in acute ischemic stroke. There are limited data on tenecteplase 0.4 mg/kg in patients with increased stroke severity. We aimed to assess safety and efficacy of tenecteplase 0.4 mg/kg in patients with moderate and severe ischemic stroke. Methods- NOR-TEST (Norwegian Tenecteplase Stroke Trial) was a phase III trial designed to investigate the safety and efficacy of tenecteplase 0.4 mg/kg versus alteplase 0.9 mg/kg in ischemic stroke. In this post hoc analysis, moderate stroke was defined as admission National Institutes of Health Stroke Scale; 6 to 14 and severe stroke as National Institutes of Health Stroke Scale; ≥15. Rates of favorable outcome at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality after 7 and 90 days were assessed. Results- In patients with moderate stroke (n=261), there were no differences in rates of favorable outcome, sICH, or mortality between tenecteplase and alteplase. In patients with severe stroke (n=87), there were no differences in outcome, frequency of sICH, or mortality at 7 days, but all-cause mortality at 90 days was increased in patients treated with tenecteplase (10 [26.3%] versus 4 [9.1%]; P=0.045). One patient died of sICH in the tenecteplase group, and 2 patients died of sICH in the alteplase group. Conclusions- Rates of favorable outcome and sICH were similar between treatment groups in patients with moderate and severe stroke. Mortality after 90 days was increased in patients with severe stroke receiving tenecteplase. Future studies assessing tenecteplase 0.4 mg/kg should monitor safety parameters closely in patients with severe stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

Tenecteplase Versus Alteplase Between 3 and 4.5 Hours in Low National Institutes of Health Stroke Scale.

Background and Purpose- Thrombolysis with alteplase has beneficial effect on outcome and is safe within 4.5 hours. The present study compares the efficacy and safety of tenecteplase and alteplase in patients treated 3 to 4.5 hours after ischemic stroke. Methods- The data are from a prespecified substudy of patients included in The NOR-TEST (Norwegian Tenecteplase Stroke Trial), a randomized control trial comparing tenecteplase with alteplase. Results- The median admission National Institutes of Health Stroke Scale for this study population was 3 (interquartile range, 2-6). In the intention-to-treat analysis, 57% of patients that received tenecteplase and 53% of patients that received alteplase reached good functional outcome (modified Rankin Scale score of 0-1) at 3 months (odds ratio, 1.19; 95% CI, 0.68-2.10). The rates of intracranial hemorrhage in the first 48 hours were 5.7% in the tenecteplase group and 6.7% in the alteplase group (odds ratio, 0.84; 95% CI, 0.26-2.70). At 3 months, mortality was 5.7% and 4.5%, respectively. After excluding stroke mimics and patients with modified Rankin Scale score of >1 before stroke, the proportion of patients with good functional outcome was 61% in the tenecteplase group and 57% in the alteplase group (odds ratio, 1.24; 95% CI, 0.65-2.37). Conclusions- Tenecteplase is at least as effective as alteplase to achieve a good clinical outcome in patients with mild stroke treated between 3 and 4.5 hours after ischemic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.