BackgroundAdipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for advanced cell-based therapies. They are routinely obtained enzymatically from fat lipoaspirate (LP) as SVF, and may undergo prolonged ex vivo expansion, with significant senescence and decline in multipotency. Besides, these techniques have complex regulatory issues, thus incurring in the compelling requirements of GMP guidelines. Hence, availability of a minimally manipulated, autologous adipose tissue would have remarkable biomedical and clinical relevance. For this reason, a new device, named Lipogems® (LG), has been developed. This ready-to-use adipose tissue cell derivate has been shown to have in vivo efficacy upon transplantation for ischemic and inflammatory diseases. To broaden our knowledge, we here investigated the angiogenic and anti-inflammatory properties of LG and its derived MSC (LG-MSCs) population.MethodsHuman LG samples and their LG-MSCs were analyzed by immunohistochemistry for pericyte, endothelial and mesenchymal stromal cell marker expression. Angiogenesis was investigated testing the conditioned media (CM) of LG (LG-CM) and LG-MSCs (LG-MSCs-CM) on cultured endothelial cells (HUVECs), evaluating proliferation, cord formation, and the expression of the adhesion molecules (AM) VCAM-1 and ICAM-1. The macrophage cell line U937 was used to evaluate the anti-inflammatory properties, such as migration, adhesion on HUVECs, and release of RANTES and MCP-1.ResultsOur results indicate that LG contained a very high number of mesenchymal cells expressing NG2 and CD146 (both pericyte markers) together with an abundant microvascular endothelial cell (mEC) population. Substantially, both LG-CM and LG-MSC-CM increased cord formation, inhibited endothelial ICAM-1 and VCAM-1 expression following TNFα stimulation, and slightly improved HUVEC proliferation. The addition of LG-CM and LG-MSC-CM strongly inhibited U937 migration upon stimulation with the chemokine MCP-1, reduced their adhesion on HUVECs and significantly suppressed the release of RANTES and MCP-1.ConclusionsOur data indicate that LG micro-fragmented adipose tissue retains either per se, or in its embedded MSCs content, the capacity to induce vascular stabilization and to inhibit several macrophage functions involved in inflammation.
Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery‐related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer‐reviewed, English publications reporting post‐CABG delirium or cognitive decline data, for at least one risk factor. Random‐effects meta‐analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety‐seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1–6 months) post‐CABG cognitive decline. Conclusions This meta‐analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. Registration URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42020149276.
Background Apathy is a frequent and underrecognized neurological disorder symptom. Reduced goal-directed behavior caused by apathy is associated with poor outcomes for older adults in residential aged care. Recommended nonpharmacological treatments include person-centered therapy using information and communication technology. Virtual reality (VR) in the form of head-mounted displays (HMDs) is a fully immersive technology that provides access to a wide range of freely available content. The use of VR as a therapy tool has demonstrated promise in the treatment of posttraumatic stress disorder and anxiety. In addition, VR has been used to improve conditions including depression, anxiety, cognitive function, and balance in older adults with memory deficits, Alzheimer disease, and Parkinson disease. Research using VR for the symptoms of apathy in older adults living in residential aged care facilities is limited. Objective This study aims to examine whether using HMDs as a tool for reminiscence therapy improves the symptoms of apathy compared with using a laptop computer and physical items with older adults living in residential aged care. Methods In this multisite trial, 43 participants were allocated to one of three groups: reminiscence therapy intervention using VR in the form of HMDs, reminiscence therapy using a laptop computer supplemented by physical items if required (active control), and a usual care (passive control) group. The primary outcome was apathy, and the secondary outcomes included cognition and depression. The side effects of using HMDs were also measured in the VR group. Results Mixed model analyses revealed no significant group interaction over time in outcomes between the VR and laptop groups (estimate=−2.24, SE 1.89; t40=−1.18; P=.24). Pooled apathy scores in the two intervention groups compared with the passive control group also revealed no significant group interaction over time (estimate=−0.26, SE 1.66; t40=−0.16; P=.88). There were no significant secondary outcomes. Most participants in the VR group stated that they would prefer to watch content in VR than on a flat screen (Χ22=11.2; P=.004), side effects from HMD use were negligible to minimal according to the Simulator Sickness Questionnaire cutoff scores. Conclusions Although there were no significant results in outcome measures, this study found that participants engaged in the research and enjoyed the process of reminiscing using both forms of technology. It was found that VR can be implemented in an aged care setting with correct protocols in place. Providing residents in aged care with a choice of technology may assist in increasing participation in activities. We cannot dismiss the importance of immediate effects while the therapy was in progress, and this is an avenue for future research. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12619001510134; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378564. International Registered Report Identifier (IRRID) RR2-DOI: 10.1136/bmjopen-2020-046030
Very few double-blind trials of oral immunotherapy have been reported. The majority of these have been performed with pollen extracts and the results have often been equivocal. The major weaknesses of these studies have been the short periods of the trials, the low doses of allergen employed and inadequate evaluation of efficacy. The present study has involved a placebo-controlled double-blind trial of oral immunotherapy for three years with Dermatophagoides pteronyssinus at relatively high doses in 18 paediatric patients. Throughout the trial clinical parameters (symptom and medication scores) and immunological parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess the safety and efficacy of the treatment. The treatment was well tolerated by all patients and no side-effects were experienced. Clinical improvement was evident after the second year of therapy and this was confirmed by a significant reduction in conjunctival reactivity assessed by a specific conjunctival provocation test. In addition, there were significant changes in the immunological parameters with a reduction in specific IgE and increased levels of IgG4 and IgG1, results in keeping with previous studies of oral and subcutaneous immunotherapy. Although the results do not provide an explanation of the basis of successful oral immunotherapy, they clearly demonstrate the efficacy and safety of the treatment and suggest that it may be a useful and more acceptable alternative for patients than the traditional subcutaneous immunotherapy.
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