PRediction of acute coronary syndrome in acute ischemic StrokE (PRAISE) – protocol of a prospective, multicenter trial with central reading and predefined endpoints

Background: Current guidelines recommend measurement of troponin in acute ischemic stroke (AIS) patients. In AIS patients, troponin elevation is associated with increased mortality and worse outcome. However, uncertainty remains regarding the underlying pathophysiology of troponin elevation after stroke, particularly regarding diagnostic and therapeutic consequences. Troponin elevation may be caused by coronary artery disease (CAD) and more precisely acute coronary syndrome (ACS). Both have a high prevalence in stroke patients and contribute to poor outcome. Therefore, better diagnostic algorithms are needed to identify those AIS patients likely to have ACS or other manifestations of CAD. Methods/design: The primary goal of the "PRediction of Acute coronary syndrome in acute Ischemic StrokE" (PRAISE) study is to develop a diagnostic algorithm for prediction of ACS in AIS patients. The primary hypothesis will test whether dynamic high-sensitivity troponin levels determined by repeat measurements (i.e., "rise or fall-pattern") indicate presence of ACS when compared to stable (chronic) troponin elevation. PRAISE is a prospective, multicenter, observational trial with central reading and predefined endpoints guided by a steering committee. Clinical symptoms, troponin levels as well as findings on electrocardiogram, echocardiogram, and coronary angiogram will be recorded and assessed by central academic core laboratories. Diagnosis of ACS will be made by an endpoint adjudication committee. Severe adverse events will be evaluated by a critical event committee. Safety will be judged by a data and safety monitoring board. Follow-up will be conducted at three and twelve months and will record new vascular events (i.e., stroke and myocardial infarction) as well as death, functional and cognitive status. According to sample size calculation, 251 patients have to be included. Discussion: PRAISE will prospectively determine the frequency of ACS and characterize cardiac and coronary pathologies in a large, multicenter cohort of AIS patients with troponin elevation. The findings will elucidate the origin of troponin elevation, shed light on its impact on necessary diagnostic procedures and provide data on the safety and diagnostic yield of coronary angiography early after stroke. Thereby, PRAISE will help to refine algorithms and develop guidelines for the cardiac workup in AIS. Trial registration: NCT03609385 registered 1st August 2018

Stroke admissions, stroke severity, and treatment rates in urban and rural areas during the COVID-19 pandemic

Background: Many regions worldwide reported a decline of stroke admissions during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. It remains unclear whether urban and rural regions experienced similar declines and whether deviations from historical admission numbers were more pronounced among specific age, stroke severity or treatment groups.Methods: We used registry datasets from (a) nine acute stroke hospitals in Berlin, and (b) nine hospitals from a rural TeleNeurology network in Northeastern Germany for primary analysis of 3-week-rolling average of stroke/TIA admissions before and during the COVID-19 pandemic. We compared course of stroke admission numbers with regional cumulative severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) infections. In secondary analyses, we used emergency department logs of the Berlin Charite University hospital to investigate changes in age, stroke severity, and thrombolysis/thrombectomy frequencies during the early regional Sars-CoV-2 spread (March and April 2020) and compared them with preceding years.Results: Compared to past years, stroke admissions decreased by 20% in urban and 20-25% in rural hospitals. Deviations from historical averages were observable starting in early March and peaked when numbers of regional Sars-CoV-2 infections were still low. At the same time, average admission stroke severity and proportions of moderate/severe strokes (NIHSS >5) were 20 and 20-40% higher, respectively. There were no relevant deviations observed in proportions of younger patients (<65 years), proportions of patients with thrombolysis, or number of thrombectomy procedures. Stroke admissions at Charite subsequently rebounded and reached near-normal levels after 4 weeks when the number of new Sars-CoV-2 infections started to decrease.Conclusions: During the early pandemic, deviations of stroke-related admissions from historical averages were observed in both urban and rural regions of Northeastern Germany and appear to have been mainly driven by avoidance of admissions of mildly affected stroke patients.Clinical epidemiolog

Type 1 Myocardial Infarction in Patients With Acute Ischemic Stroke

Importance : Elevated values of high-sensitivity cardiac troponin (hs-cTn) are common in patients with acute ischemic stroke and are associated with poor prognosis. However, diagnostic and therapeutic implications in patients with ischemic stroke remain unclear. Objective : To identify factors indicative of myocardial infarction (MI) in patients with acute ischemic stroke and hs-cTn elevation. The primary hypothesis was that a dynamic change of hs-cTn values (>50% change) in patients with acute ischemic stroke indicates MI. Design, Setting, and Participants : This cross-sectional study was a prospective, observational study with blinded end-point assessment conducted across 26 sites in Germany. Patients were included if they had acute ischemic stroke within 72 hours and either (1) highly elevated hs-cTn values on admission (>52 ng/L) or (2) hs-cTn levels above the upper limit of normal and a greater than 20% change at repeated measurements. Patients were enrolled between August 2018 and October 2020 and had 1 year of follow-up. Statistical analysis was performed between April 2022 and August 2023. Exposure : Standardized electrocardiography, echocardiography, and coronary angiography. Main Outcome and Measures : Diagnosis of MI as adjudicated by an independent end-point committee based on the findings of electrocardiography, echocardiography, and coronary angiography. Results : In total, 254 patients were included. End points were adjudicated in 247 patients (median [IQR] age, 75 [66-82] years; 117 were female [47%] and 130 male [53%]). MI was present in 126 of 247 patients (51%) and classified as type 1 MI in 50 patients (20%). Dynamic change in hs-cTn value was not associated with MI in univariable (32% vs 38%; χ2 P = .30) or adjusted comparison (odds ratio, 1.05; 95% CI, 0.31-3.33). The baseline absolute hs-cTn value was independently associated with type 1 MI. The best cutoffs for predicting type 1 MI were at hs-cTn values 5 to 10 times the upper limit normal. Conclusions and Relevance : This study found that in patients with acute ischemic stroke, a dynamic change in hs-cTn values did not identify MI, underscoring that dynamic changes do not identify the underlying pathophysiological mechanism. In exploratory analyses, very high absolute hs-cTn values were associated with a diagnosis of type 1 MI. Further studies are needed how to best identify patients with stroke who should undergo coronary angiography

Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-modulating stromal components

While cancer-associated stroma (CAS) in malignant tumours is well described, stromal changes in benign forms of naturally occurring tumours remain poorly characterized. Spontaneous canine mammary carcinomas (mCA) are viewed as excellent models of human mCA. We have recently reported highly conserved stromal reprogramming between canine and human mCA based on transcriptome analysis of laser-capture-microdissected FFPE specimen. To identify stromal changes between benign and malignant mammary tumours, we have analysed matched normal and adenoma-associated stroma (AAS) from 13 canine mammary adenomas and compared them to previous data from 15 canine mCA. Our analyses reveal distinct stromal reprogramming even in small benign tumours. While similarities between AAS and CAS exist, the stromal signature clearly distinguished adenomas from mCA. The distinction between AAS and CAS is further substantiated by differential enrichment in several hallmark signalling pathways as well as differential abundance in cellular composition. Finally, we identify COL11A1, VIT, CD74, HLA-DRA, STRA6, IGFBP4, PIGR, and TNIP1 as strongly discriminatory stromal genes between adenoma and mCA, and demonstrate their prognostic value for human breast cancer. Given the relevance of canine CAS as a model for the human disease, our approach identifies disease-modulating stromal components with implications for both human and canine breast cancer

Three-dimensional bio-printing and bone tissue engineering: technical innovations and potential applications in maxillofacial reconstructive surgery

Background Bone grafting has been considered the gold standard for hard tissue reconstructive surgery and is widely used for large mandibular defect reconstruction. However, the midface encompasses delicate structures that are surrounded by a complex bone architecture, which makes bone grafting using traditional methods very challenging. Three-dimensional (3D) bioprinting is a developing technology that is derived from the evolution of additive manufacturing. It enables precise development of a scaffold from different available biomaterials that mimic the shape, size, and dimension of a defect without relying only on the surgeon’s skills and capabilities, and subsequently, may enhance surgical outcomes and, in turn, patient satisfaction and quality of life. Review This review summarizes different biomaterial classes that can be used in 3D bioprinters as bioinks to fabricate bone scaffolds, including polymers, bioceramics, and composites. It also describes the advantages and limitations of the three currently used 3D bioprinting technologies: inkjet bioprinting, micro-extrusion, and laser-assisted bioprinting. Conclusions Although 3D bioprinting technology is still in its infancy and requires further development and optimization both in biomaterials and techniques, it offers great promise and potential for facial reconstruction with improved outcome

Ischemic Stroke Prevention in Patients Atrial Fibrillation and a Recent Ischemic Stroke, TIA, or Intracranial Hemorrhage; a World Stroke Organisation (WSO) Scientific Statement.

BACKGROUND: Secondary stroke prevention in patients with atrial fibrillation (AF) is one of the fastest growing areas in the field of cerebrovascular diseases. This Scientific statement from the World Stroke Organization Brain & Heart Task Force provides a critical analysis of the strength of current evidence this topic, highlights areas of current controversy, identifies knowledge gaps, and proposes priorities for future research. METHODS: We select topics with the highest clinical relevance and perform a systematic search to answer specific practical questions. Based on the strength of available evidence and knowledge gaps, we identify topics that need to be prioritized in future research. For this purpose, we adopt a novel classification of evidence strength based on the availability of publications in which the primary population is patients with recent (<6 months) cerebrovascular events, whether the primary study endpoint is a recurrent ischemic stroke, and the quality of the studies (e.g., observational vs. randomized controlled trial). SUMMARY: Priority areas include AF screening, molecular biomarkers, AF subtype classification, anticoagulation in device-detected AF, timing of anticoagulation initiation, effective management of breakthrough strokes on existing anticoagulant therapy, the role of left atrial appendage closure, novel approaches, and antithrombotic therapy post-intracranial hemorrhage. Strength of currently available evidence varies across the selected topics, with early anticoagulation being the one showing more consistent data. CONCLUSION: Several knowledge gaps persist in most areas related to secondary stroke prevention in AF. Prioritizing research in this field is crucial to advance current knowledge and improve clinical care

Ischemic stroke prevention in patients with atrial fibrillation and a recent ischemic stroke, TIA, or intracranial hemorrhage: A World Stroke Organization (WSO) scientific statement

Background: Secondary stroke prevention in patients with atrial fibrillation (AF) is one of the fastest growing areas in the field of cerebrovascular diseases. This scientific statement from the World Stroke Organization Brain & Heart Task Force provides a critical analysis of the strength of current evidence on this topic, highlights areas of current controversy, identifies knowledge gaps, and proposes priorities for future research. Methods: We select topics with the highest clinical relevance and perform a systematic search to answer specific practical questions. Based on the strength of available evidence and knowledge gaps, we identify topics that need to be prioritized in future research. For this purpose, we adopt a novel classification of evidence strength based on the availability of publications in which the primary population is patients with recent (<6 months) cerebrovascular events, the primary study endpoint is a recurrent ischemic stroke, and the quality of the studies (e.g. observational versus randomized controlled trial). Summary: Priority areas include AF screening, molecular biomarkers, AF subtype classification, anticoagulation in device-detected AF, timing of anticoagulation initiation, effective management of breakthrough strokes on existing anticoagulant therapy, the role of left atrial appendage closure, novel approaches, and antithrombotic therapy post-intracranial hemorrhage. Strength of currently available evidence varies across the selected topics, with early anticoagulation being the one showing more consistent data. Conclusion: Several knowledge gaps persist in most areas related to secondary stroke prevention in AF. Prioritizing research in this field is crucial to advance current knowledge and improve clinical care.Graphical abstractLASACCJFSM

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis: Individual Patient Data Meta-Analysis

BACKGROUND AND PURPOSE: We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. METHODS: We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). RESULTS: In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). CONCLUSIONS: Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke

Clonagem de canistel por estaquia

The yellow sapote is native to southern Mexico and Central America, and its fruits have high content of carotenoids and vitamin A. Its propagation is done through seed, resulting in considerable genetic variability among individuals, being preferable vegetative propagation, in order to fix desirable characteristics. Thus, the aim of this study was to evaluate the vegetative propagation by cuttings of semiherbaceous branches of yellow sapote, according to four genotypes and four concentrations of IBA. Cuttings were semi-herbaceous apical, maintained with a pair of leaves, under intermittent mist for 120 days. A completely randomized experimental design was use, in a 4×4 factorial (yellow sapote genotypes × IBA concentrations) with four replicates and ten cuttings per plot. It was evaluate the percentage of survival, leaf retention, rooting, callus, average number and length of roots per cutting. The PC-1 genotype was superior to others in all variables, with emphasis on the rooting of cuttings exceeding 60%. The IBA concentrations (0; 1,000; 3,000 and 5,000 mg L-1) did not influence survival, leaf retention and rooting but increased the number and length of roots compared to control treatment (without IBA). There were differences in rooting capacity to among genotypes of yellow sapote, being the best response obtained with PC-1. The IBA concentration 3,000 mg L-1 results in greater number and length of roots in the yellow sapote cuttings.O canistel é nativo do sul do México e América Central e seus frutos apresentam elevado teor de carotenoides e vitamina A. Sua propagação é feita via sementes, resultando em considerável variabilidade genética entre os indivíduos, sendo a propagação vegetativa preferível, a fim de fixar características desejáveis. Assim, o objetivo deste trabalho foi avaliar a propagação vegetativa por estaquia de ramos semi-herbáceos de canistel, em função de quatro genótipos e quatro concentrações de AIB. Foram utilizadas estacas semiherbáceas apicais, mantidas com um par de folhas, sob nebulização intermitente, por 120 dias. O delineamento experimental foi o inteiramente casualizado, em esquema fatorial 4×4 (genótipos de canistel × concentrações de AIB), com quatro repetições e dez estacas por parcela. Foram avaliados a porcentagem de sobrevivência, a retenção foliar, o enraizamento, o calejamento, o número e o comprimento médio de raízes por estaca. O genótipo PC-1 foi superior aos demais, em todas as variáveis avaliadas, com destaque para o enraizamento das estacas, superior a 60%. As concentrações de AIB (0; 1.000; 3.000 e 5.000 mg L-1) não influenciaram na sobrevivência, retenção foliar e enraizamento das estacas, mas aumentaram o número e o comprimento de raízes em relação ao tratamento-controle (sem AIB). Há diferença na capacidade de enraizamento das estacas entre os genótipos de canistel, sendo a melhor resposta obtida com PC-1. A concentração de 3.000 mg L-1 de AIB resulta em maior número e comprimento de raízes nas estacas de canistel.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Estadual Paulista Faculdade de Ciências Agrárias e VeterináriasAgência de Desenvolvimento Agrário e Extensão Rural de Mato Grosso do Sul Centro de Pesquisa e Capacitação da AgraerUniversidade Estadual Paulista Faculdade de Ciências Agrárias e Veteriná riasUniversidade Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Produção VegetalUniversidade Estadual Paulista Faculdade de Ciências Agrárias e VeterináriasUniversidade Estadual Paulista Faculdade de Ciências Agrárias e Veteriná riasUniversidade Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Produção Vegeta