5366 research outputs found
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Manipulation of lipid metabolism during normothermic machine perfusion: Effect of defatting therapies on donor liver functional recovery.
No full textBACKGROUND
Strategies to increase steatotic donor livers' utilisation are required to tackle the mortality on the transplant waiting list. We aimed to test the efficacy of pharmacological enhancement of the lipid metabolism of human livers during ex-situ normothermic machine perfusion to promote defatting and improve the functional recovery of the organs.
METHODS
Ten livers discarded because of steatosis were allocated to a defatting group that had the perfusate supplemented with a combination of drugs to enhance lipid metabolism or a control group that received perfusion fluid with vehicle only. Steatosis was assessed using tissue homogenate and histological analysis. Markers for lipid oxidation and solubilisation, oxidative injury, inflammation and biliary function were evaluated by ELISA, immunohistochemistry and in-gel protein detection.
RESULTS
Treatment reduced tissue triglycerides by 38% and macrovesicular steatosis by 40% over 6 hours. This effect was driven by increased solubilisation of triglycerides (p=0.04); and mitochondrial oxidation as assessed by increased ketogenesis (p=0.008) and adenosine triphosphate synthesis (p=0.01) associated with raised levels of the enzymes ACOX-1, CPT1A and acetyl-CoA synthetase. Concomitantly, defatted livers exhibited enhanced metabolic functional parameters such as urea production (p=0.03), lower vascular resistance, lower release of alanine aminotransferase (p=0.049) and higher bile production (p=0.008) with a higher bile pH (p=0.03). The treatment downregulated the expression of markers for oxidative injury, activation of immune cells (CD-14; CD-11b) and reduced the release of inflammatory cytokines in the perfusate (TNF-α; IL-1β).
CONCLUSION
Pharmacological enhancement of intracellular lipid metabolism during normothermic machine perfusion decreased the lipid content of human livers within 6 hours. It also improved the intracellular metabolic support to the organs leading to successful functional recovery and decreased expression of markers of reperfusion injury. This article is protected by copyright. All rights reserved
Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time-dependent analysis.
No full textAIMS
To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes.
METHODS
People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA included as a time-dependent variable was fitted to these data.
RESULTS
Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002-1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03-1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA .
CONCLUSIONS
In people with newly diagnosed Type 1 diabetes, higher HbA is associated with an increased risk for fractures. This article is protected by copyright. All rights reserved
Review article: managing the adverse events caused by anti-TNF therapy in inflammatory bowel disease.
No full textBACKGROUND
Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti-TNF therapies. Biosimilar anti-TNF monoclonal antibodies are increasingly used. Anti-TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately.
AIM
To cover the range of potential adverse reactions as a result of biologic therapy and specifically management of these events.
METHODS
A Medline and Pubmed search was undertaken. Search terms included were "anti-TNF," "infliximab" or "adalimumab" or "golimumab" combined with the keywords "ulcerative colitis" or "Crohn's disease" or "inflammatory bowel disease" and then narrowed to articles containing the keywords "complications," "side effects" or "adverse events" or "safety profile." International guidelines were also reviewed where relevant.
RESULTS
Adverse events discussed in this review include infusion reactions, blood disorders and infections (including bacterial, viral, fungal and opportunistic infections) as well as autoimmune, dermatological disorders, cardiac and neurological conditions. Malignancies including solid organ, haematological and those linked to viral disease are discussed.
CONCLUSIONS
Anti-TNF therapy has wide-ranging effects on the immune system resulting in a spectrum of potential adverse events in a small proportion of patients. Research advances are improving the understanding, recognition and management of these adverse events
Endoscopic findings of checkpoint inhibitor-induced ileitis with use of the latest advanced endoscopic optical diagnosis: near-focus narrow-band imaging.
No full text
Slowly progressive distal muscle weakness: neuropathy or myopathy?
No full textNonaka myopathy is an autosomal recessive and slowly progressive distal myopathy. It is part of a rare group of myopathies predominantly affecting the distal limb musculature. Over 150 cases have been reported across the Middle East, Japan and Europe. We report the case of a 33-year-old woman presenting with symmetrical upper and lower limb weakness, most severely affecting the distal muscle groups. After extensive neurological investigation including neurophysiology, muscle biopsy and genetic analysis, she was finally diagnosed with Nonaka myopathy and treated conservatively with physiotherapy
Erratum: Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases.
No full text
Online and Social Media Footprint of All Swedish Aesthetic Plastic Surgeons.
No full textBACKGROUND
The visual nature of the Internet and its newer technologies makes it naturally aligned to plastic and aesthetic surgery. While many studies have looked at the use of social media ('SoMe'), they have been limited by either low response rate or limited scope. Our aim was to analyse a whole community of aesthetic plastic surgeons and their use of the Internet and social media platforms over a period of many years.
METHODS
All active members of the Swedish national aesthetic plastic surgery society were identified. Webpages, professional (LinkedIn), social media (Facebook, Twitter, Instagram) and video-sharing (YouTube) accounts as well as online patient forum (Plastikoperationsforum) mentions of the surgeons and their clinics were identified, and corresponding platform-specific metrics were analysed.
RESULTS
Of the 85 active members, 67 (78.9%) had a webpage on one of the 34 different clinic websites. The websites of older established clinics had a significantly better Alexa ranking than newer ones. Surgeons with a profile on Facebook or Instagram were significantly younger than those without an account. Twitter was the least preferred social media platform. Each surgeon had a mean 12.8 threads per year as compared to a mean 34.3 threads per clinic per year.
CONCLUSION
Most of the new practices established by Swedish aesthetic plastic surgeons in the last 10 years are single-surgeon ones. Instagram and Facebook accounts of their clinics seem to be the most popular SoMe platforms. Younger surgeons were more likely to have a Facebook or Instagram account and to be using two or more social media platforms. These data provide information about all aesthetic plastic surgeons registered with the Swedish national body and their increasing use of SoMe.
LEVEL OF EVIDENCE V
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266