Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease, and is strongly associated with the metabolic syndrome. In the last decade, it has become apparent that the ...clinical burden of NAFLD is not restricted to liver‐related morbidity or mortality, and the majority of deaths in NAFLD patients are related to cardiovascular disease (CVD) and cancer. These findings have fuelled concerns that NAFLD may be a new, and added risk factor for extrahepatic diseases such as CVD, chronic kidney disease (CKD), colorectal cancer, endocrinopathies (including type 2 diabetes mellitus T2DM and thyroid dysfunction), and osteoporosis. In this review we critically appraise key studies on NAFLD‐associated extrahepatic disease. There was marked heterogeneity between studies in study design (cross‐sectional versus prospective; sample size; presence/absence of well‐defined controls), population (ethnic diversity; community‐based versus hospital‐based cohorts), and method of NAFLD diagnosis (liver enzymes versus imaging versus biopsy). Taking this into account, the cumulative evidence to date suggests that individuals with NAFLD (specifically, nonalcoholic steatohepatitis) harbor an increased and independent risk of developing CVD, T2DM, CKD, and colorectal neoplasms. We propose future studies are necessary to better understand these risks, and suggest an example of a screening strategy. (Hepatology 2014;59:1174–1197)
The evolution of mobile phone technology has introduced new possibilities to the field of medicine. Combining technological advances with medical expertise has led to the use of mobile phones in all ...healthcare areas including diagnostics, telemedicine, research, reference libraries and interventions. This article provides an overview of the peer -reviewed literature, published between 1 August 2006 and 1 August 2011, for the application of mobile/cell phones (from basic text-messaging systems to smartphones) in healthcare in both resource-poor and high-income countries. Smartphone use is paving the way in high-income countries, while basic text-messaging systems of standard mobile phones are proving to be of value in low- and middle-income countries. Ranging from infection outbreak reporting, anti-HIV therapy adherence to gait analysis, resuscitation training and radiological imaging, the current uses and future possibilities of mobile phone technology in healthcare are endless. Multiple mobile phone based applications are available for healthcare workers and healthcare consumers; however, the absolute majority lack an evidence base. Therefore, more rigorous research is required to ensure that healthcare is not flooded with non-evidence based applications and is maximized for patient benefit.
These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) ...of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.
Patients with liver cirrhosis and, in particular, those with liver failure are at high risk of reduced muscle mass and strength/function, otherwise known as sarcopenia. Sarcopenia is a complex, ...multifactorial (poor nutritional intake, protein catabolism, physical inactivity) chronic condition, which increases the risk of liver-related morbidity and mortality. Early recognition and tailored management incorporating high protein diets and combination aerobic/resistance exercise can ameliorate the complications associated with sarcopenia in cirrhosis. This review provides an overview of the epidemiology, pathogenesis, assessment tools and management of sarcopenia in cirrhosis.
Due to the potential impact on the diagnosis and treatment of various cardiovascular diseases, work on the rheology of blood has significantly expanded in the last decade, both experimentally and ...theoretically. Experimentally, blood has been confirmed to demonstrate a variety of non-Newtonian rheological characteristics, including pseudoplasticity, viscoelasticity, and thixotropy. New rheological experiments and the development of more controlled experimental protocols on more extensive, broadly physiologically characterized, human blood samples demonstrate the sensitivity of aspects of hemorheology to several physiological factors. For example, at high shear rates the red blood cells elastically deform, imparting viscoelasticity, while at low shear rates, they form "rouleaux" structures that impart additional, thixotropic behavior. In addition to the advances in experimental methods and validated data sets, significant advances have also been made in both microscopic simulations and macroscopic, continuum, modeling, as well as novel, multiscale approaches. We outline and evaluate the most promising of these recent developments. Although we primarily focus on human blood rheology, we also discuss recent observations on variations observed across some animal species that provide some indication on evolutionary effects.
Smoking, both by donors and by recipients, has a major impact on outcomes after organ transplantation. Recipients of smokers' organs are at greater risk of death (lungs hazard ratio HR, 1.36; heart ...HR, 1.8; and liver HR, 1.25), extended intensive care stays, and greater need for ventilation. Kidney function is significantly worse at 1 year after transplantation in recipients of grafts from smokers compared with nonsmokers. Clinicians must balance the use of such higher-risk organs with the consequences on waiting list mortality if the donor pool is reduced further by exclusion of such donors. Smoking by kidney transplant recipients significantly increases the risk of cardiovascular events (29.2% vs. 15.4%), renal fibrosis, rejection, and malignancy (HR, 2.56). Furthermore, liver recipients who smoke have higher rates of hepatic artery thrombosis, biliary complications, and malignancy (13% vs. 2%). Heart recipients with a smoking history have increased risk of developing coronary atherosclerosis (21.2% vs. 12.3%), graft dysfunction, and loss after transplantation. Self-reporting of smoking is commonplace but unreliable, which limits its use as a tool for selection of transplant candidates. Despite effective counseling and pharmacotherapy, recidivism rates after transplantation remain high (10-40%). Transplant services need to be more proactive in educating and implementing effective smoking cessation strategies to reduce rates of recidivism and the posttransplantation complications associated with smoking. The adverse impact of smoking by the recipient supports the requirement for a 6-month period of abstinence in lung recipients and cessation before other solid organs.
Abstract
DNA methylation is a class of epigenetic modification essential for coordinating gene expression timing and magnitude throughout normal brain development and for proper brain function ...following development. Aberrant methylation changes are associated with changes in chromatin architecture, transcriptional alterations and a host of neurological disorders and diseases. This review highlights recent advances in our understanding of the methylome's functionality and covers potential new roles for DNA methylation, their readers, writers, and erasers. Additionally, we examine novel insights into the relationship between the methylome, DNA–protein interactions, and their contribution to neurodegenerative diseases. Lastly, we outline the gaps in our knowledge that will likely be filled through the widespread use of newer technologies that provide greater resolution into how individual cell types are affected by disease and the contribution of each individual modification site to disease pathogenicity.
Characterizing human blood, a complex material with a spectrum of thixo-elasto-visco-plastic properties, through the development of more effective and efficient models has achieved special interest ...of late. This effort details the development a new approach, the tensorial-enhanced-Thixo-Visco-Plastic model (t-e-TVP), which integrates elements from the proven Bingham and generalized Maxwell systems to create a more robust framework and subsequently cast into a tensorial format. Here, the elastic and viscoelastic stress contributions from the microstructure are superimposed upon the viscoelastic backbone solution for stress offered by the modified TVP frame. The utility of this novel model is tested against the contemporary tensorial-ethixo-mHAWB (t-ethixo-mHAWB) framework, a similar model with a greater number of parameters, using rheological data of human blood collected on an ARESG2 strain-controlled rheometer. The blood samples are parametrically and statistically analyzed, entailing the comparison of the t-e-TVP and t-ethixo-mHAWB models with their capacity to accurately predict small and large amplitude oscillatory shear as well as unidirectional large amplitude oscillatory shear flow in blood.
Summary
Background
Physical frailty is common in chronic liver disease and the setting of liver transplantation. It is associated with poor quality of life, increased hospitalisation and mortality. ...Despite this, the impact of exercise in these patients remains poorly understood.
Aim
To summarise the impact of physical exercise on physical frailty in patients with chronic liver disease until after liver transplantation.
Methods
A MEDLINE and PubMed search was undertaken using the terms; “physical activity”, “functional capacity”, “exercise”, “prehabilitation”, “frailty”, “liver cirrhosis”, “liver failure”, “liver transplantation” “chronic liver disease” and “end‐stage liver disease” from January 1990 to June 2019.
Results
Eleven studies (five randomised controlled, five observational, one case study) demonstrated that exercise improves VO2 peak, anaerobic threshold, 6‐minute walk distance, muscle mass/function and quality of life in patients with compensated and decompensated cirrhosis. Improvements were most significant with a combination of aerobic and resistance exercises at moderate‐high intensity. The studies were small (n = 1‐50) and mainly focused on supervised, hospital‐based exercises, excluding patients with significant liver failure (MELD > 12). Seven studies (four randomised controlled and three observational) demonstrated that predominantly supervised (only one home‐based) aerobic exercise after liver transplantation improves aerobic capacity, muscle mass/strength and quality of life. There was marked heterogeneity in timing, intensity and type of exercises.
Conclusion
Exercise improves key components of physical frailty (functional/aerobic capacity, sarcopenia) and quality of life in chronic liver disease and after liver transplantation. Understanding the type, compliance, intensity and duration of exercise and its impact on hard clinical outcomes should be the focus of future large controlled clinical trials.
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