Influence of vascular imaging acquisition at local stroke centers on workflows in the drip-n-ship model: a RACECAT post hoc analysis.

BACKGROUND: The influence of vascular imaging acquisition on workflows at local stroke centers (LSCs) not capable of performing thrombectomy in patients with a suspected large vessel occlusion (LVO) stroke remains uncertain. We analyzed the impact of performing vascular imaging (VI+) or not (VI- at LSC arrival on variables related to workflows using data from the RACECAT Trial. OBJECTIVE: To compare workflows at the LSC among patients enrolled in the RACECAT Trial with or without VI acquisition. METHODS: We included patients with a diagnosis of ischemic stroke who were enrolled in the RACECAT Trial, a cluster-randomized trial that compared drip-n-ship versus mothership triage paradigms in patients with suspected acute LVO stroke allocated at the LSC. Outcome measures included time metrics related to workflows and the rate of interhospital transfers and thrombectomy among transferred patients. RESULTS: Among 467 patients allocated to a LSC, vascular imaging was acquired in 277 patients (59%), of whom 198 (71%) had a LVO. As compared with patients without vascular imaging, patients in the VI+ group were transferred less frequently as thrombectomy candidates to a thrombectomy-capable center (58% vs 74%, P=0.004), without significant differences in door-indoor-out time at the LSC (median minutes, VI+ 78 (IQR 69-96) vs VI- 76 (IQR 59-98), P=0.6). Among transferred patients, the VI+ group had higher rate of thrombectomy (69% vs 55%, P=0.016) and shorter door to puncture time (median minutes, VI+ 41 (IQR 26-53) vs VI- 54 (IQR 40-70), P<0.001). CONCLUSION: Among patients with a suspected LVO stroke initially evaluated at a LSC, vascular imaging acquisition might improve workflow times at thrombectomy-capable centers and reduce the rate of futile interhospital transfers. These results deserve further evaluation and should be replicated in other settings and geographies.

Evolutionary origin, population diversity, and diagnostics for a cryptic hybrid pathogen.

Cryptic fungal pathogens pose significant identification and disease management challenges due to their morphological resemblance to known pathogenic species while harboring genetic and (often) infectionrelevant trait differences. The cryptic fungal pathogen Aspergillus latus, an allodiploid hybrid originating from Aspergillus spinulosporus and an unknown close relative of Aspergillus quadrilineatus within section Nidulantes, remains poorly understood. The absence of accurate diagnostics for A. latus has led to misidentifications, hindering epidemiological studies and the design of effective treatment plans. We conducted an in-depth investigation of the genomes and phenotypes of 44 globally distributed isolates (41 clinical isolates and three type strains) from Aspergillus section Nidulantes. We found that 21 clinical isolates were A. latus; notably, standard methods of pathogen identification misidentified all A. latus isolates. The remaining isolates were identified as A. spinulosporus (8), A. quadrilineatus (1), or A. nidulans (11). Phylogenomic analyses shed light on the origin of A. latus, indicating one or two hybridization events gave rise to the species during the Miocene, approximately 15.4 to 8.8 million years ago. Characterizing the A. latus pangenome uncovered substantial genetic diversity within gene families and biosynthetic gene clusters. Transcriptomic analysis revealed that both parental genomes are actively expressed in nearly equal proportions and respond to environmental stimuli. Further investigation into infection-relevant chemical and physiological traits, including drug resistance profiles, growth under oxidative stress conditions, and secondary metabolite biosynthesis, highlight distinct phenotypic profiles of the hybrid A. latus compared to its parental and closely related species. Leveraging our comprehensive genomic and phenotypic analyses, we propose five genomic and phenotypic markers as diagnostics for A. latus species identification. These findings provide valuable insights into the evolutionary origin, genomic outcome, and phenotypic implications of hybridization in a cryptic fungal pathogen, thus enhancing our understanding of the underlying processes contributing to fungal pathogenesis. Furthermore, our study underscores the effectiveness of extensive genomic and phenotypic analyses as a promising approach for developing diagnostics applicable to future investigations of cryptic and emerging pathogens.

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia.

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. RESULTS: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94-1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97-1.22). DISCUSSION AND CONCLUSION: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself.

First pass effect in posterior circulation occlusions: Analysis from the CICAT registry.

BACKGROUND: The first pass effect (FPE) is an independent predictor of functional independence in patients with large vessel occlusion in anterior circulation ischemic strokes. However, whether it predicts outcome in posterior circulation large vessel occlusion (PC-LVO) is uncertain. We aimed to study the frequency, characteristics, and predictors of FPE and its association with clinical outcomes in PC-LVO. METHOD: We performed an analysis from the prospective CICAT Registry. All patients with PC-LVO who underwent endovascular therapy between January 2016 and January 2020 were included. A centrally assessed clinical follow-up was performed at 3 months by blinded investigators. FPE was defined as the achievement of modified Thrombolysis In Cerebral Infarction 3 in a single pass of the endovascular thrombectomy device, and multi-pass effect (MPE) if it was achieved in more than one pass. A multivariable analysis was performed to identify whether FPE is an independent predictor of functional independence defined as a modified Rankin Score of 0-2. RESULTS: We analyzed data from 265 patients in who FPE was achieved in 105 (39.6%). Patients with FPE were more likely to achieve functional independence compared to the non-FPE group (52.4% vs 25.1%, p < .001) and the MPE group (52.4% vs 26.7%, p < .001). FPE was independently associated with functional independence (adjusted odds ratio (aOR): 2.10, 95% confidence interval (CI) 1.01-4.37) but MPE was not (aOR: 0.92, 95% CI 0.40-2.13). Independent predictors of FPE were the use of direct aspiration, embolic mechanism of stroke, and the absence of general anesthesia (GA) use. CONCLUSIONS: FPE is an independent predictor of functional independence in PC-LVO and was associated with a significantly better outcome than MPE.

Evolution of quality indicators in acute stroke during the RACECAT Trial: Impact in the general population.

BACKGROUND: Acute ischemic stroke patients not referred directly to a comprehensive stroke center (CSC) have reduced access to endovascular treatment (EVT). The RACECAT trial is a population-based cluster-randomized trial, designed to compare mothership and drip-and-ship strategies in acute ischemic stroke patients outside the catchment area of a CSC. AIMS: To analyze the evolution of performance indicators in the regions that participated in RACECAT. METHODS: This retrospective longitudinal observational study included all stroke alerts evaluated by emergency medical services in Catalonia between February 2016 and February 2020. Cases were classified geographically according to the nearest SC: local SC (Local-SC) and CSC catchment areas. We analyzed the evolution of EVT rates and relevant workflow times in Local-SC versus CSC catchment areas over three study periods: P1 (February 2016 to April 2017: before RACECAT initiation), P2 (May 2017 to September 2018), and P3 (October 2018 to February 2020). RESULTS: We included 20603 stroke alerts, 10,694 (51.9%) of which were activated within Local-SC catchment areas. The proportion of patients receiving EVT within Local-SC catchment areas increased (P1 vs. P3: 7.5% (95% confidence interval (CI), 6.4-8.7) to 22.5% (95% CI, 20.8-24.4) p < 0.001). Inequalities in the odds of receiving EVT were reduced for patients from CSC versus Local-SC catchment areas (P1: odds ratio (OR) 3.9 (95% CI, 3.2-5) vs. P3: OR 1.5 (95% CI, 1.3-1.7) In Local-SC, door-to-image (P1: 24 (interquartile range (IQR) 15-36), P2: 24 (15-35), P3: 21 (13-32) min, p < 0.001) and door-to-needle times (P1: 42 (31-60), P2: 41 (29-58), P3: 35 (25-50) p < 0.001) reduced. Time from Local-SC arrival to groin puncture also decreased over time (P1: 188 [151-229], P2: 190 (157-233), P3: 168 (127-215) min, p < 0.001). CONCLUSION: An increase in EVT rates in Local-SC regions with a significant decrease in workflow times occurred during the period of the RACECAT trial.

Determinants and Trends of the Use of Intravenous Thrombolysis for Minor Stroke: A Population-Based Study, 2016 to 2020.

BACKGROUND: We analyzed the main factors associated with intravenous thrombolysis (IVT) in patients with minor ischemic stroke. METHODS: Data were obtained from a prospective, government-mandated, population-based registry of stroke code patients in Catalonia (6 Comprehensive Stroke Centers, 8 Primary Stroke Centers, and 14 TeleStroke Centers). We selected patients diagnosed with ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) ≤5 at hospital admission from January 2016 to December 2020. We excluded patients with a baseline modified Rankin Scale score of ≥3, absolute contraindication for IVT, unknown stroke onset, or admitted to hospital beyond 4.5 after stroke onset. The main outcome was treatment with IVT. We performed univariable and binary logistic regression analyses to identify the most important factors associated with IVT. RESULTS: We included 2975 code strokes; 1433 (48.2%) received IVT of which 30 (2.1%) had a symptomatic hemorrhagic transformation. Patients treated with IVT as compared to patients who did not receive IVT were more frequently women, had higher NIHSS, arrived earlier to hospital, were admitted to a Comprehensive Stroke Centers, and had large vessel occlusion. After binary logistic regression, NIHSS score 4 to 5 (odds ratio, 40.62 [95% CI, 31.73-57.22]; P<0.001) and large vessel occlusion (odds ratio, 16.39 [95% CI, 7.25-37.04]; P<0.001) were the strongest predictors of IVT. Younger age, female sex, baseline modified Rankin Scale score of 0, earlier arrival to hospital (<120 minutes after stroke onset), and the type of stroke center were also independently associated with IVT. The weight of large vessel occlusion on IVT was higher in patients with lower NIHSS. CONCLUSIONS: Minor stroke female patients, with higher NIHSS, arriving earlier to the hospital, presenting with large vessel occlusion and admitted to a Comprehensive Stroke Centers were more likely to receive intravenous thrombolysis.

Transcriptional Regulation by the Velvet Protein VE-1 during Asexual Development in the Fungus Neurospora crassa.

Asexual reproduction in fungi facilitates the dispersal and colonization of new substrates and, in pathogenic fungi, allows infection of plants and animals. The velvet complex is a fungus-specific protein complex that participates in the regulation of gene expression in response to environmental signals like light, as well as developmental processes, pathogenesis, and secondary metabolism. The velvet complex in the fungus Neurospora crassa is composed of three proteins, VE-1, VE-2, and LAE-1. Mutations in ve-1 or ve-2, but not in lae-1, led to shorter heights of aerial tissue, a mixture of aerial hyphae and developing macroconidia, and increased microconidiation when they were combined with mutations in the transcription factor gene fl. VE-2 and LAE-1 were detected during vegetative growth and conidiation, unlike VE-1, which was mostly observed in samples obtained from submerged vegetative hyphae. We propose that VE-1 is the limiting component of the velvet complex during conidiation and has a major role in the transcriptional regulation of conidiation. Characterization of the role of VE-1 during mycelial growth and asexual development (conidiation) by transcriptome sequencing (RNA-seq) experiments allowed the identification of a set of genes regulated by VE-1 that participate in the regulation of conidiation, most notably the transcription factor genes vib-1 and fl. We propose that VE-1 and VE-2 regulate the development of aerial tissue and the balance between macro- and microconidiation in coordination with FL and VIB-1. IMPORTANCE Most fungi disperse in nature and infect new hosts by producing vegetative spores or conidia during asexual development. This is a process that is regulated by environmental signals like light and the availability of nutrients. A protein complex, the velvet complex, participates in the integration of environmental signals to regulate conidiation. We have found that a key component of this complex in the fungus Neurospora crassa, VE-1, has a major role in the regulation of transcription during conidiation. VE-1 regulates a large number of genes, including the genes for the transcription factors FL and VIB-1. Our results will help to understand how environmental signals are integrated in the fungal cell to regulate development.

The Fungal Protein Mes1 Is Required for Morphogenesis and Virulence in the Dimorphic Phytopathogen Ustilago maydis.

Polarized growth is a defining property of filamentous fungi, which plays an important role in different aspects of their biology, including virulence. However, little information is available about the determinants of cell surface organization and their role in polarized growth. The fungal protein MesA was identified in a genetic screen in Aspergillus nidulans and is involved in the stabilization of the polarity axes, but it has no evident role in budding yeast. In this work, I present evidence that in the dimorphic fungal phytopathogen Ustilago maydis MesA/Mes1 is involved in cell wall stability and polarized growth. mes1 mutants were more sensitive to drugs provoking cell wall stress, and they displayed a temperature-sensitive phenotype. Actin cytoskeleton was disorganized in a mes1 mutant, suggesting that there is a connection between Mes1, the actin cytoskeleton and polarized morphogenesis. The septin ring was also absent from the bud tip, but not the bud neck. Deletion of mes1 provoked defects in endocytosis and vacuolar organization in the cells. Mes1 was essential for strong polarized growth in the hyphal form, but it was dispensable during low or moderate polarized growth in the yeast form in U. maydis at a permissive temperature. Consistently, mes1 mutants showed delayed mating and they were avirulent.

Light regulates the degradation of the regulatory protein VE-1 in the fungus Neurospora crassa.

BACKGROUND: Fungi use light as an environmental signal to regulate developmental transitions that are key aspects of their biological cycles and that are also relevant for their dispersal and infectivity as plant or animal pathogens. In addition, light regulates the accumulation of photoprotective pigments, like carotenoids, and other secondary metabolites. Most fungal light responses occur after changes in gene transcription and we describe here a novel effect of light in the regulation of degradation of VE-1, a key component of the velvet complex, in the model fungus Neurospora crassa. The velvet complex is a fungal-specific protein complex that coordinates fungal development, secondary metabolism, and light regulation by interacting with other regulators and photoreceptors and modifying gene expression. RESULTS: We have characterized the role of VE-1 during conidiation in N. crassa. In vegetative mycelia, VE-1 is localized in the cytoplasm and nuclei and is required for light-dependent transcription but does not interact with the photoreceptor and transcription factor WC-1. VE-1 is more stable in light than in darkness during asexual development (conidiation). We have shown that this light effect requires the blue-light photoreceptor WC-1. We have characterized the role of the proteasome, the COP9 signalosome (CSN), and the adaptor component of cullin-RING ubiquitin ligases, FWD-1, in the degradation of VE-1. CONCLUSIONS: We propose that this new effect of light allows the fungal cell to adapt quickly to changes in light exposure by promoting the accumulation of VE-1 for the regulation of genes that participate in the biosynthesis of photoprotective pigments.

Identification of an acetyl esterase in the supernatant of the environmental strain Bacillus sp. HR21-6.

Bacillus sp. HR21-6 is capable of the chemo- and regioselective synthesis of lipophilic partially acetylated phenolic compounds derived from olive polyphenols, which are powerful antioxidants important in the formulation of functional foods. In this work, an acetyl esterase was identified in the secretome of this strain by non-targeted proteomics, and classified in the GDSL family (superfamily SGNH). The recombinant protein was expressed and purified from Escherichia coli in the soluble form, and biochemically characterized. Site-directed mutagenesis was performed to understand the role of different amino acids that are conserved among GDSL superfamily of esterases. Mutation of Ser-10, Gly-45 or His-185 abolished the enzyme activity, while mutation of Asn-77 or Thr-184 altered the substrate specificity of the enzyme. This new enzyme is able to perform chemoselective conversions of olive phenolic compounds with great interest in the food industry, such as hydroxytyrosol, 3,4-dihydroxyphenylglycol, and oleuropein.

Predictors of Functional Outcome After Thrombectomy in Patients With Prestroke Disability in Clinical Practice.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) in ischemic stroke patients with poor prestroke conditions remains controversial. We aimed to analyze the frequency of previously disabled patients treated with MT in clinical practice, the safety and clinical response to MT of patients with preexisting disability, and the disabled patient characteristics associated with a better response to MT. METHODS: We studied all consecutive patients with anterior circulation occlusion treated with MT from January 2017 to December 2019 included in the Codi Ictus Catalunya registry-a government-mandated, prospective, hospital-based data set. Prestroke disability was defined as modified Rankin Scale score 2 or 3. Functional outcome at 90 days was centrally assessed by a blinded evaluator of the Catalan Stroke Program. Favorable outcome (to return at least to prestroke modified Rankin Scale at 90 days) and safety and secondary outcomes were compared with patients without previous disability. Logistic regression analysis was used to assess the association between prestroke disability and outcomes and to identify a disabled patient profile with favorable outcome after MT. RESULTS: Of 2487 patients included in the study, 409 (17.1%) had prestroke disability (313 modified Rankin Scale score 2 and 96 modified Rankin Scale score 3). After adjustment for covariates, prestroke disability was not associated with a lower chance of achieving favorable outcome at 90 days (24% versus 30%; odds ratio, 0.79 [0.57-1.08]), whereas it was independently associated with a higher risk of symptomatic intracranial hemorrhage (5% versus 3%; odds ratio, 2.04 [1.11-3.72]) and long-term mortality (31% versus 18%; odds ratio, 1.74 [1.27-2.39]) compared with patients without disability. Prestroke disabled patients without diabetes, Alberta Stroke Program Early CT Score >8 and National Institutes of Health Stroke Scale score <17 showed similar safety and outcome results after MT as patients without prestroke disability. CONCLUSIONS: Despite a higher mortality and risk of symptomatic intracranial hemorrhage, prestroke-disabled patients return as often as independent patients to their prestroke level of function, especially those nondiabetic patients with favorable early ischemic signs profile. These data support a potential benefit of MT in patients with previous mild or moderate disability after large anterior vessel occlusion stroke.

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry.

BACKGROUND AND PURPOSE:  In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. METHODS:  Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). RESULTS:  Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). CONCLUSIONS:  Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Evidence for an arginine-dependent route for the synthesis of NO in the model filamentous fungus Aspergillus nidulans.

Nitric oxide (NO) is a signalling molecule in eukaryotic and prokaryotic organisms. NO levels transiently boost upon induction of conidiation in Aspergillus nidulans. Only one pathway for NO synthesis involving nitrate reductase has been reported in filamentous fungi so far, but this does not satisfy all the NO produced in fungal cells. Here we provide evidence for at least one additional biosynthetic pathway in A. nidulans involving l-arginine or an intermediate metabolite as a substrate. Under certain growth conditions, the addition of l-arginine to liquid media elicited a burst of NO that was not dependent on any of the urea cycle genes. The NO levels were controlled by the metabolically available arginine, which was regulated by mobilization from the vacuoles and during development. In vitro assays with protein extracts and amino acid profiling strongly suggested the existence of an arginine-dependent NO pathway analogous to the mammalian NO synthase. Addition of polyamines induced NO synthesis, and mutations in the polyamine synthesis genes puA and spdA reduced the production of NO. In conclusion, here we report an additional pathway for the synthesis of NO in A. nidulans using urea cycle intermediates.

Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia.

INTRODUCTION: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. METHODS: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. RESULTS: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. CONCLUSION: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately.

Blood Biomarker Panels for the Early Prediction of Stroke-Associated Complications.

Background Acute decompensated heart failure (ADHF) and respiratory tract infections (RTIs) are potentially life-threatening complications in patients experiencing stroke during hospitalization. We aimed to test whether blood biomarker panels might predict these complications early after admission. Methods and Results Nine hundred thirty-eight patients experiencing ischemic stroke were prospectively recruited in the Stroke-Chip study. Post-stroke complications during hospitalization were retrospectively evaluated. Blood samples were drawn within 6 hours after stroke onset, and 14 biomarkers were analyzed by immunoassays. Biomarker values were normalized using log-transformation and Z score. PanelomiX algorithm was used to select panels with the best accuracy for predicting ADHF and RTI. Logistic regression models were constructed with the clinical variables and the biomarker panels. The additional predictive value of the panels compared with the clinical model alone was evaluated by receiver operating characteristic curves. An internal validation through a 10-fold cross-validation with 3 repeats was performed. ADHF and RTI occurred in 19 (2%) and 86 (9.1%) cases, respectively. Three-biomarker panels were developed as predictors: vascular adhesion protein-1 >5.67, NT-proBNP (N-terminal pro-B-type natriuretic peptide) >4.98 and d-dimer >5.38 (sensitivity, 89.5%; specificity, 71.7%) for ADHF; and interleukin-6 >3.97, von Willebrand factor >3.67, and d-dimer >4.58 (sensitivity, 82.6%; specificity, 59.8%) for RTI. Both panels independently predicted stroke complications (panel for ADHF: odds ratio [OR] [95% CI], 10.1 [3-52.2]; panel for RTI: OR, 3.73 [1.95-7.14]) after adjustment by clinical confounders. The addition of the panel to clinical predictors significantly improved areas under the curve of the receiver operating characteristic curves in both cases. Conclusions Blood biomarkers could be useful for the early prediction of ADHF and RTI. Future studies should assess the usefulness of these panels in front of patients experiencing stroke with respiratory symptoms such as dyspnea.

Impact of general anesthesia on posterior circulation large vessel occlusions after endovascular thrombectomy.

BACKGROUND: The impact of general anesthesia on functional outcome in patients with large vessel occlusion remains unclear. Most studies have focused on anterior circulation large vessel occlusion; however, little is known about the effect of general anesthesia in patients with posterior circulation-large vessel occlusion. METHODS: We performed a retrospective analysis from the prospective CICAT registry. All patients with posterior circulation-large vessel occlusion-and undergoing endovascular therapy between January 2016 and January 2020 were included. Demographics, baseline characteristics, procedural data, and anesthesia modality (general anesthesia or conscious sedation) were evaluated. The primary outcome was the proportion of patients with good clinical outcome (modified Rankin Scale score of 0-2) at three months. RESULTS: 298 patients underwent endovascular treatment with posterior circulation-large vessel occlusion-were included. Age, diabetes mellitus, renal insufficiency, baseline National Institutes of Health Stroke Scale score, puncture to recanalization length, ≥3 device passes, absent of successful recanalization (defined as treatment in cerebral ischemia of 3), and general anesthesia were statistically associated with poor outcome (mRS: 3-6). In the multivariable regression, general anesthesia and ≥3 device passes were independently associated with poor outcome (aOR: 3.11, (95% CI: 1.34-7.2); P = 0.01 and 3.77, (95% CI: 1.29-11.01); P = 0.02, respectively). Patients treated with general anesthesia were less likely to have a good outcome at three months compared to conscious sedation (19.7% vs. 45.1%, P < 0.001). CONCLUSIONS: In our study population, general anesthesia use is associated with poor clinical outcome in patients with posterior circulation-large vessel occlusion-treated endovascularly.

An arsRB resistance operon confers tolerance to arsenite in the environmental isolate Terribacillus sp. AE2B 122.

Terribacillus sp. AE2B 122 is an environmental strain isolated from olive-oil agroindustry wastes. This strain displays resistance to arsenic, one of the most ubiquitous carcinogens found in nature. Terribacillus sp. AE2B 122 possesses an unusual ars operon, consisting of the transcriptional regulator (arsR) and arsenite efflux pump (arsB) but no adjacent arsenate reductase (arsC) locus. Expression of arsR and arsB was induced when Terribacillus was exposed to sub-lethal concentrations of arsenate. Heterologous expression of the arsB homologue in Escherichia coli∆arsRBC demonstrated that it conferred resistance to arsenite and reduced the accumulation of arsenic inside the cells. Two members of the arsC-like family (Te3384 and Te2854) found in the Terribacillus genome were not induced by arsenic, but their heterologous expression in E. coli ∆arsC and ∆arsRBC increased the accumulation of arsenic in both strains. We found that both Te3384 and Te2854 slightly increased resistance to arsenate in E. coli ∆arsC and ∆arsRBC, possibly by chelation of arsenic or by increasing the resistance to oxidative stress. Finally, arsenic speciation assays suggest that Terribacillus is incapable of arsenate reduction, in agreement with the lack of an arsC homologue in the genome.

Vascular Occlusion Evolution in Endovascular Reperfusion Candidates Transferred from Primary to Comprehensive Stroke Centers.

BACKGROUND: The evolution of the symptomatic intracranial occlusion during transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) for endovascular treatment (EVT) is not widely known. Our aim was to identify factors related to partial or complete recanalization (REC) at CSC arrival in patients with a documented large vessel occlusion (LVO) in PSC transferred for EVT evaluation to better define the workflow at CSC of this group of patients. METHODS: We conducted an observational, multicenter study from a prospective, government-mandated, population-based registry of stroke patients with documented LVO at PSC transferred to CSC for EVT from January 2017 to June 2019. The primary end point was defined as partial or complete REC that precluded EVT at CSC arrival (REC). We evaluated the association between baseline, treatment variables and time intervals with the presence of REC. RESULTS: From 589 patients, the rate of REC at CSC was 10.5% in all LVO patients transferred from PSC to CSC for EVT evaluation. On univariate analysis, lower PSC-NIHSS (median 12vs.16, p = 0.001), tPA treatment at PSC (13.7 vs. 5.0%; p = 0.001), presence of M2 occlusion on PSC (16.8 vs. 9%; p = 0.023), and clinical improvement at CSC arrival (21.7 vs. 9.6% p = 0.001) were associated with REC at CSC. On multivariate analysis, clinical improvement at CSC arrival (p < 0.001, OR: 5.96 95% CI: 2.5-13.9) and PSC tPA treatment predicted REC (p = 0.003, OR: 4.65, 95% CI: 1.73-12.4). CONCLUSION: REC at CSC arrival occurs exceptionally in patients with a documented LVO on PSC. Repeating a second vascular study before EVT would not be necessary in most patients. Despite its modest effect, tPA treatment at PSC was an independent predictor of REC.

Blood biomarkers predictive of epilepsy after an acute stroke event.

OBJECTIVE: Blood biomarkers have not been widely investigated in poststroke epilepsy. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and analyze their association with the development of epilepsy at long term. METHODS: A panel of 14 blood biomarkers was evaluated in patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z-scores. Stroke and epilepsy-related variables were also assessed: stroke severity, determined by National Institutes of Health Stroke Scale (NIHSS) score, stroke type and cause, time from stroke to onset of late seizures, and type of seizure. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with epilepsy. RESULTS: From a cohort of 1115 patients, 895 patients were included. Mean ± standard deviation (SD) age was 72.0 ± 13.1 years, and 57.8% of patients were men. Fifty-one patients (5.7%) developed late seizures, with a median time to onset of 232 days (interquartile range [IQR] 86-491). NIHSS score ≥8 (P < .001, hazard ratio [HR] 4.013, 95% confidence interval [CI] 2.123-7.586) and a history of early onset seizures (P < .001, HR 4.038, 95% CI 1.802-9.045) were factors independently associated with a risk of developing epilepsy. Independent blood biomarkers predictive of epilepsy were high endostatin levels >1.203 (P = .046, HR 4.300, 95% CI 1.028-17.996) and low levels of heat shock 70 kDa protein-8 (Hsc70) <2.496 (P = .006, HR 3.795, 95% CI 1.476-9.760) and S100B <1.364 (P = .001, HR 2.955, 95% CI 1.534-5.491). The risk of epilepsy when these biomarkers were combined increased to 17%. The area under the receiver-operating characteristic (ROC) curve of the predictive model was stronger when clinical variables were combined with blood biomarkers (74.3%, 95% CI 65.2%-83.3%) than when they were used alone (68.9%, 95% CI 60.3%-77.6%). SIGNIFICANCE: Downregulated S100B and Hsc70 and upregulated endostatin may assist in prediction of poststroke epilepsy and may provide additional information to clinical risk factors. In addition, these data are hypothesis-generating for the epileptogenic process.