• Whitehead Gibbons posted an update 6 months ago

    Vessel damage is a general pathological process in many neurodegenerative disorders, as well as spinal cord injury, stroke, or trauma. Biomaterials can present novel tools to repair and regenerate damaged vessels. The aim of the present study is to test collagen hydrogels loaded with different angiogenic factors to study vessel repair in organotypic brain slice cultures. In the experimental set up I, we made a cut on the organotypic brain slice and tested re-growth of laminin + vessels. In the experimental set up II, we cultured two half brain slices with a gap with a collagen hydrogel placed in between to study endothelial cell migration. In the experimental set up I, we showed that the number of vessels crossing the cut was tendencially increased with the addition of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor, or platelet-derived growth factor-BB compared to the control group. In the experimental set up II, we demonstrated that a collagen hydrogel loaded with FGF-2 resulted in a significantly increased number of migrated laminin + cells in the gap between the slices compared to the control hydrogel. Co-administration of several growth factors did not further potentiate the effects. Taken together, we show that organotypic brain slices are good models to study brain vessels and FGF-2 is a potent angiogenic factor for endothelial cell proliferation and migration. Our results provide evidence that the collagen hydrogels can be used as an extracellular matrix for the vascular endothelial cells.

    The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials.

    In DAPA-CKD, 4304 participants with a urinary albumincreatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol).

    Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), ofety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.

    Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.

    Infections caused by triazole drug-resistant Aspergillus fumigatus are an increasing problem. The sensitivity of standard culture is poor, abrogating susceptibility testing. Early detection of resistance can improve patient outcomes, yet tools for this purpose are limited.

    To develop and validate a pyrosequencing technique to detect resistance-conferring cyp51A polymorphisms from clinical respiratory specimens and A. fumigatus isolates.

    Method validation was performed by Sanger sequencing and pyrosequencing of 50 A. fumigatus isolates with a spectrum of triazole susceptibility patterns. Then, 326 Aspergillus quantitative PCR (qPCR)-positive respiratory samples collected over a 27 month period (January 2017-March 2019) from 160 patients at the UK National Aspergillosis Centre were assessed by cyp51A pyrosequencing. The Sanger sequencing and pyrosequencing results were compared with those from high-volume culture and standard susceptibility testing.

    The cyp51A genotypes of the 50 isolates analysed by pythod allowed prompt recognition of resistance and the selection of appropriate antifungal treatment when culture was negative.

    Despite recent advances in catheter ablation for atrial fibrillation (AF), pulmonary vein reconnection (PVR), and AF recurrence remain significantly high. Ablation index (AI) is a new method incorporating contact force, time, and power that should optimize procedural outcomes. We aimed to evaluate the efficacy and safety of AI-guided catheter ablation compared to a non-AI-guided approach.

    A systematic search was performed on MEDLINE (via PubMED), EMBASE, COCHRANE, and European Society of Cardiology (ESC) databases (from inception to 1 July 2019). We included only studies that compared AI-guided with non-AI-guided catheter ablation of AF. Eleven studies reporting on 2306 patients were identified. Median follow-up period was 12 months. Ablation index-guided ablation had a significant shorter procedural time (141.0 vs. 152.8 min, P = 0.01; I2 = 90%), ablation time (21.8 vs. 32.0 min, P < 0.00001; I2 = 0%), achieved first-pass isolation more frequently and was less frequently associated with acute PVR (OR = 0.37, 95%CI 0.18-0.75; 18.0% vs 35.0%; P = 0.006; I2 = 0%). Importantly, atrial arrhythmia relapse post-blanking was significantly lower in AI compared to non-AI catheter ablation (OR = 0.41, 95%CI 0.25-0.66; 11.8% vs. 24.9%, P = 0.0003; I2 = 35%). Finally, there was no difference in complication rate between AI and non-AI ablation, with the number of cardiac tamponade events in the AI group less being numerically lower (OR = 0.69, 95%CI 0.30-1.60, 1.6% vs. Atglistatin 2.5%, P = 0.39; I2 = 0%).

    These data suggest that AI-guided catheter ablation is associated with increased efficacy of AF ablation, while preserving a comparable safety profile to non-AI catheter ablation.

    These data suggest that AI-guided catheter ablation is associated with increased efficacy of AF ablation, while preserving a comparable safety profile to non-AI catheter ablation.

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