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

Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke and High Cerebral Microbleed Burden: A Meta-analysis.

IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with ≥4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95% CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95% CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95% CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95% CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95% CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence of CMB and high CMB burdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS

New remote cerebral microbleeds in acute ischemic stroke: an analysis of the randomized, placebo-controlled WAKE-UP trial

No abstract available

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

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

Characteristics associated with occurrence of stroke in patients with infective endocarditis – a retrospective cohort study

Abstract Background Stroke is a severe complication of infective endocarditis (IE), associated with high rates of mortality. Data on how IE patients with and without stroke differ may help to improve understanding contributing mechanisms. Methods All patients treated for IE between 2019 and 2021 with and without associated stroke were identified from the medical records of three academic tertiary care hospitals in Germany, all part of Charité – Universitätsmedizin Berlin, Germany. Multivariable logistic regression analyses were performed to identify variables associated with the occurrence of stroke. Results The study population consisted of 353 patients diagnosed with IE. Concomitant stroke occurred in 96/353 (27.2%) patients. Acute stroke was independently associated with co-occurring extracerebral arterial embolism [adjusted Odds ratio (aOR = 2.52; 95% confidence interval (CI) 1.35–4.71)], acute liver failure (aOR = 2.62; 95% CI 1.06–6.50), dental focus of infection (aOR = 3.14; 95% CI 1.21–8.12) and left-sided IE (aOR = 28.26; 95% CI 3.59-222.19). Stroke was found less often in IE patients with congenital heart disease (aOR = 0.20; 95% CI 0.04–0.99) and atypical pathogens isolated from blood culture (aOR = 0.31; 95% CI 0.14–0.72). Conclusions Stroke is more likely to occur in individuals with systemic complications affecting other organs, too. Special attention should be addressed to dental status. The low incidence of stroke in patients with congenital heart disease may reflect awareness and prophylactic measures