Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: a pooled analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

A journey through bacterial colonies

This photograph originally appeared in the 2014 Research student photography and image competition held to celebrate National Science Week (Aug 16-24). Blurb: The image is a highly magnified photograph of the fibres of a wound dressing, false coloured in violet, colonised by wound bacteria (rod-shape cells, false coloured in brown). The mechanisms of interactions of bacteria with fibrous substrates are still poorly understood. My research shows that bacteria tend to cover the surface of the fibres and proliferate in the interspaces of the dressing. Bacteria colonising the empty spaces among fibres are glued together and proliferate following a spiral route, from the fibre surface towards the middle of the interspaces, leaving a progressively smaller “black holeâ€\u9d in the centre

Development of electrospun dressings for infected wounds

Chronic wounds show incomplete healing processes and expose patients to high risk of infection. These wounds are painful, debilitating and are estimated to affect almost 500,000 Australians. One major challenge associated to chronic wound management consists in limiting the bacterial load in the wound bed. A fibrous mesh capable of actively cleaning the wound from bacteria was designed by tuning fibre size and surface chemistry. Bacteria are attracted from the wound bed towards the fibres and they remain trapped within the fibrous network. The antibacterial action of a chemical coating deposed onto the fibres ensures that trapped bacteria are progressively killed

Bacterial response to different surface chemistries fabricated by plasma polymerization on electrospun nanofibers

Control over bacterial attachment and proliferation onto nanofibrous materials constitutes a major challenge for a variety of applications, including filtration membranes, protective clothing, wound dressings, and tissue engineering scaffolds. To develop effective devices, the interactions that occur between bacteria and nanofibers with different morphological and physicochemical properties need to be investigated. This paper explores the influence of fiber surface chemistry on bacterial behavior. Different chemical functionalities were generated on the surface of electrospun polystyrene nanofibers through plasma polymerization of four monomers (acrylic acid, allylamine, 1,7-octadiene, and 1,8-cineole). The interactions of Escherichia coli with the surface modified fibers were investigated through a combination of scanning electron microscopy and confocal laser scanning microscopy. Fiber wettability, surface charge, and chemistry were found to affect the ability of bacterial cells to attach and proliferate throughout the nanofiber meshes. The highest proportion of viable cells attachment occurred on the hydrophilic amine rich coating, followed by the hydrophobic octadiene. The acrylic acid coating rich in carboxyl groups showed a s can be strategically tuned to control bacterial behavior

Electrospun polystyrene fiber diameter influencing bacterial attachment, proliferation, and growth

Electrospun materials have been widely investigated in the past few decades as candidates for tissue engineering applications. However, there is little available data on the mechanisms of interaction of bacteria with electrospun wound dressings of different morphology and surface chemistry. This knowledge could allow the development of effective devices against bacterial infections in chronic wounds. In this paper, the interactions of three bacterial species (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) with electrospun polystyrene meshes were investigated. Bacterial response to meshes with different fiber diameters was assessed through a combination of scanning electron microscopy (SEM) and confocal microscopy. Experiments included attachment studies in liquid medium but also directly onto agar plates; the latter was aimed at mimicking a chronic wound environment. Fiber diameter was shown to affect the ability of bacteria to proliferate within the fibrous networks, depending on cell size and shape. The highest proliferation rates occurred when fiber diameter was close to the bacterial size. Nanofibers were found to induce conformational changes of rod shaped bacteria, limiting the colonization process and inducing cell death. The data suggest that simply tuning the morphological properties of electrospun fibers may be one strategy used to control biofilm formation within wound dressings

Electrospun nanofibers as dressings for chronic wound care: advances, challenges, and future prospects

Chronic non-healing wounds show delayed and incomplete healing processes and in turn expose patients to a high risk of infection. Treatment currently focuses on dressings that prevent microbial infiltration and keep a balanced moisture and gas exchange environment. Antibacterial delivery from dressings has existed for some time, with responsive systems now aiming to trigger release only if infection occurs. Simultaneously, approaches that stimulate cell proliferation in the wound and encourage healing have been developed. Interestingly, few dressings appear capable of simultaneously impairing or treating infection and encouraging cell proliferation/wound healing. Electrospinning is a simple, cost-effective, and reproducible process that can utilize both synthetic and natural polymers to address these specific wound challenges. Electrospun meshes provide high-surface area, micro-porosity, and the ability to load drugs or other biomolecules into the fibers. Electrospun materials have been used as scaffolds for tissue engineering for a number of years, but there is surprisingly little literature on the interactions of fibers with bacteria and co-cultures of cells and bacteria. This Review examines the literature and data available on electrospun wound dressings and the research that is required to develop smart multifunctional wound dressings capable of treating infection and healing chronic wounds

Tailored functionalization of poly(L-lactic acid) substrates at the nanoscale to enhance cell response

Poly(L-lactic) acid (PLLA) has been widely employed in tissue engineering due to its mechanical properties, biodegradability and biocompatibility. The layer-by-layer (LbL) technique was here proposed as a simple method to impart bioactivity to the surface of PLLA substrates. Aminolysis treatment was applied to introduce amino groups on the surface of PLLA solvent cast films. Then, PLLA films were coated with heparin (HE)/chitosan (CH) multilayer by the LbL technique. Each functionalization step was characterized through physico-chemical and morphological analyses. Aminolysis treatment increased film surface wettability (64.8\ub0 \ub1 2.4\ub0 against 74.6\ub0 \ub1 1.3\ub0 for untreated PLLA) due to the formation of surface amino groups, which were quantified by acid orange colorimetric assay (0.05\u2009nmol/mm2). After the deposition of 9 layers, the static contact angle varied between values close to 40\ub0 C (HE-based layer) and 60\u2009\ub0C (CH-based layer), showing the typical alternate trend of LbL coating. The successful HE/CH deposition was confirmed by ATR-FTIR and X-ray photoelectron spectroscopy (XPS) analyses. Particularly, XPS spectra of coated samples showed the presence of nitrogen (indicative of HE and CH deposition), and sulfur (indicative of HE deposition). The amount of deposited HE was quantified by Taylor's Blue colorimetric method, after the deposition of 19 and 20 layers the HE concentration was around 33 \ub5g/cm2. Finally, in vitro studies performed using HaCaT immortalized human skin keratinocytes, C2C12 immortalized mouse myoblasts and human fibroblasts demonstrated that HE/CH multilayer-coated PLLA is a promising substrate for soft tissue engineering, as cell response may be modulated by changing the surface chemical properties