Reprogramming : evolving path to functional surrogate β-Cells

Numerous cell sources are being explored to replenish functional β-cell mass since the proof-of -concept for cell therapy of diabetes was laid down by transplantation of islets. Many of these cell sources have been shown to possess a degree of plasticity permitting differentiation along new lineages into insulin-secreting β-cells. In this review, we explore emerging reprograming pathways that aim to generate bone fide insulin producing cells. We focus on small molecules and key transcriptional regulators that orchestrate phenotypic conversion and maintenance of engineered cells

Pharmacogenomics of hepatitis C infections: personalizing therapy

It is a widely held view that drug response genes have not proved as useful in clinical practice as anticipated at the start of the genomic era. An exception is in the treatment for chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon α and ribavirin. In 2009, four independent genome-wide analyses identified IL28B polymorphisms that predict drug response in chronic hepatitis C (CHC). This discovery had immediate clinical impact. First, the IL28B genotype could be used to personalize therapy. In the 2 years since discovery, most of the more than 100,000 CHC patients commencing therapy for CHC in the West will have considered IL28B genotype testing. Second, the discovery has supported clinical trials for the use of the protein encoded by the gene known as interferon lambda. Third, it is expected that new insights into HCV pathogenesis will follow from studies of how IL28B affects HCV viral clearance and, ultimately, this will lead to new therapeutic strategies for CHC. This review discusses how IL28B genotyping is now used in personalizing therapy and, with the dramatically changing clinical landscape in CHC, with the advent of direct-acting antivirals, the prospects ahead

Evolution of risk prediction models for post-operative mortality in patients with cirrhosis

The perception of high surgical risk among patients with cirrhosis has resulted in a long-standing reluctance to operate. Risk stratification tools, first implemented over 60 years ago, have attempted to assess mortality risk among cirrhotic patients and ensure the best possible outcomes for this difficult to treat cohort. Existing postoperative risk prediction tools including the Child–Turcotte–Pugh (CTP) and Model for End-stage Liver Disease (MELD) provide some prediction of risk in counselling patients and their families but tend to overestimate surgical risk. More personalised prediction algorithms such as the Mayo Risk Score and VOCAL-Penn score that incorporate surgery-specific risks have demonstrated a significant improvement in prognostication and can ultimately aid multidisciplinary team determination of potential risks. The development of future risk scores will need to incorporate, first and foremost, predictive efficacy, but perhaps just as important is the feasibility and usability by front-line healthcare professionals to ensure timely and efficient prediction of risk for cirrhotic patients

Depression, anxiety and stress among patients with inflammatory bowel disease during the COVID-19 pandemic : Australian national survey

Background: The global COVID-19 pandemic has impacted on the mental health of individuals, particularly those with chronic illnesses. We aimed to quantify stress, anxiety and depression among individuals with Inflammatory bowel disease (IBD) in Australia during the pandemic. Methods: An electronic survey was made available to IBD patients Australia-wide from 17 June to 12 July 2020. Respondents with an underlying diagnosis of IBD and over 18 years of age were included. A validated questionnaire (Depression, Anxiety, Stress Score-21, DASS21) was used to assess depression, anxiety and stress. Data on potential predictors of depression, anxiety and stress were collected. Results: 352 participated in the survey across Australia. 60.5% of respondents fulfilled DASS criteria for at least moderate depression, anxiety or stress. 45% reported a pre-existing diagnosis of depression and/or anxiety. Over 2/3 of these respondents reported worsening of their pre-existing depression/anxiety due to the current pandemic. Of those without a pre-existing diagnosis of anxiety or depression, high rates of at least moderate to severe depression (34.9%), anxiety (32.0%) and stress (29.7%) were noted. Younger age (OR 0.96, 95% CI 0.94 to 0.98, p<0.001), lack of access to an IBD nurse (OR 1.81, 95% CI 1.03 to 3.19, p=0.04) and lack of education on reducing infection risk (OR 1.99, 95% CI 1.13 to 3.50, p=0.017) were associated with significant stress, anxiety and/or depression. Conclusion: High prevalence of undiagnosed depression, anxiety and stress was identified among respondents. Improved access to IBD nurse support and greater attention to education are modifiable factors that may reduce depression, anxiety and/or stress among patients with IBD during the pandemic

The role of micronutrients in the infection and subsequent response to hepatitis C virus

Micronutrient deficiencies develop for a variety of reasons, whether geographic, socioeconomic, nutritional, or as a result of disease pathologies such as chronic viral infection. As micronutrients are essential for a strong immune response, deficiencies can significantly dampen both the innate and the adaptive arms of antiviral immunity. The innate immune response in particular is crucial to protect against hepatitis C virus (HCV), a hepatotropic virus that maintains chronic infection in up to 80% of individuals if left untreated. While many micronutrients are required for HCV replication, an overlapping group of micronutrients are also necessary to enact a potent immune response. As the liver is responsible for the storage and metabolism of many micronutrients, HCV persistence can influence the micronutrients’ steady state to benefit viral persistence both directly and by weakening the antiviral response. This review will focus on common micronutrients such as zinc, iron, copper, selenium, vitamin A, vitamin B12, vitamin D and vitamin E. We will explore their role in the pathogenesis of HCV infection and in the response to antiviral therapy. While chronic hepatitis C virus infection drives deficiencies in micronutrients such as zinc, selenium, vitamin A and B12, it also stimulates copper and iron excess; these micronutrients influence antioxidant, inflammatory and immune responses to HCV

Childhood trauma, posttraumatic stress disorder symptoms, early maladaptive schemas, and schema modes : a comparison of individuals with obesity and normal weight controls

Background: Previous research on the psychological mechanisms of obesity has primarily focused on acute psychopathology. However, there is limited literature on the role of more complex and entrenched psychological processes in weight management. The current study aimed to expand previous research by examining more enduring psychological constructs, including early maladaptive schemas (EMS), schemas modes, and trauma. Methods: Participants (N=125) comprised adults with normal weight (n=40) and obesity (n=85) from community and clinical settings in Australia. Eligible participants completed a series of self-report questionnaires via Research Electronic Data Capture (REDCap). Two, separate, one-way multivariate analysis of variance (MANOVA) were conducted to examine group differences on the outcome variables. Results: Findings indicated a significant effect of group on EMS and schema modes, V=.51, F(32, 92)=2.97, p<.001, partial η2=.51. Follow-up univariate tests revealed that individuals with obesity endorsed significantly more maladaptive schemas and schema modes and significantly less healthy schema modes than individuals with normal weight. In addition, results demonstrated a significant effect of group on childhood trauma and posttraumatic stress disorder (PTSD) symptoms, V=.19, F(6, 118)=4.70, p<.001, partial η2=.19. Subsequent univariate tests and chi-square analyses indicated that individuals with obesity reported significantly more childhood trauma as well as significantly more PTSD symptoms within the last month than normal weight individuals. Conclusion: This was the first study to compare EMS and schema modes in treatment-seeking individuals with obesity and normal weight controls using the short form version 3 of the Young Schema Questionnaire and revised, 118-item, Schema Mode Inventory. Overall, findings revealed that individuals with obesity experience more complex and enduring psychological difficulties than normal weight individuals. Increased assessment and targeted treatment of these underlying mental health concerns may contribute to a more holistic conceptualisation of obesity and could improve the long-term success of weight management

Efficacy of telephone health coaching integration with standard multidisciplinary care for adults with obesity attending a weight management service : a pilot study

Australia has one of the highest prevalences of obesity in the developed world with recognised gaps in patient access to obesity services. This non-randomised before and after study investigated the health benefits and patient acceptability of integrating the Get Healthy Service, a state-funded telephone-delivered coaching service in Australia, as an adjunct to multidisciplinary care for adults attending a public obesity service. Forty-one participants received multidisciplinary care alone while 39 participants were subsequently allocated to receive adjunctive treatment with the Get Healthy Service. Weight, body mass index, glycosylated haemoglobin, measurement of hepatic steatosis and liver enzymes were collected at baseline and 6 months. Participant evaluation was obtained post intervention. Statistically significant reductions from baseline were achieved for both control and intervention with respect to weight (−6.7 ± 2.2 kg, p = 0.01; −12.6 ± 3.2, p = 0.002), body mass index (−2.3 ± 0.8, p = 0.01; −4.8 ± 1.2 kg/m2 , p = 0.002) and glycosylated haemoglobin (−0.2 ± 0.2%, p = 0.2 (NS); −0.7 ± 0.2%, p = 0.02), respectively. There were no significant differences in steatosis or liver enzymes or in outcomes between control and intervention cohorts. A high level of patient acceptability was reported. Integrating telephone-delivered coaching provided non-inferior care and high levels of patient satisfaction. Telephone coaching aligned with the principles of an obesity service should be trialled to improve patient access to obesity interventions

Estimating the economic burden of low health literacy in the Blacktown community in Sydney, Australia : a population-based study

Evidence shows that inadequate or low health literacy (LHL) levels are significantly associated with economic ramifications at the individual, employer, and health care system levels. Therefore, this study aims to estimate the economic burden of LHL among a culturally and linguistically diverse (CALD) community in Blacktown: a local government area (LGA) in Sydney, Australia. This study is a secondary analysis of cross-sectional data from publicly available datasets, including 2011 and 2016 census data and National Health Survey (NHS) data (2017–2018) from the Australian Bureau of Statistics (ABS), and figures on Disease Expenditure in Australia for 2015–2016 provided by the Australian Institute of Health and Welfare (AIHW). This study found that 20% of Blacktown residents reported low levels of active engagement with health care providers (Domain 6 of the Health Literacy Questionnaire (HLQ)), with 14% reporting a limited understanding of the health information required to take action towards improving health or making health care decisions (Domain 9 of the HLQ). The overall extra/delta cost (direct and indirect health care costs) associated with LHL in the Blacktown LGA was estimated to be between $11,785,528 and$15,432,239 in 2020. This is projected to increase to between $18,922,844 and$24,191,911 in 2030. Additionally, the extra disability-adjusted life year (DALY) value in 2020, for all chronic diseases and age-groups—comprising the extra costs incurred due to years of life lost (YLL) and years lived with disability (YLD)—was estimated at $414,231,335. The findings of our study may enable policymakers to have a deeper understanding of the economic burden of LHL in terms of its impact on the health care system and the production economy

The use of two-dimensional shear wave elastography in people with obesity for the assessment of liver fibrosis in non-alcoholic fatty liver disease

Obesity is associated with significant comorbidities, including non-alcoholic fatty liver disease (NAFLD). Given its potential to progress to advanced liver disease, monitoring the extent and progress of liver fibrosis and assessing its fibrosis stage are essential. Although liver biopsy is considered to be the gold standard for liver fibrosis staging, it is an invasive procedure with risk of complications. Considering the rising prevalence of obesity and NAFLD globally, developing non-invasive diagnostic methods is a priority. Transient elastography (TE) is increasingly being used to assess the severity of liver disease. However, in the presence of severe obesity, the increased thickness of subcutaneous adipose tissue and changes in anatomy may affect its diagnostic accuracy. Two-dimensional shear wave elastography (2D-SWE) assesses the liver stiffness in real time along with simultaneous anatomic B-mode ultrasound imaging and allows selection of the region of interest. This would suggest that 2D-SWE has several advantages over TE in patients with severe obesity. The purpose of this review is to examine the current literature addressing the use of 2D-SWE in the assessment of liver fibrosis in patients with NAFLD. This review also examines the evidence on the use of 2D-SWE in patients with obesity and NAFLD and compares it to TE as a novel and non-invasive method of assessing liver fibrosis

The role of gut-derived microbial antigens on liver fibrosis initiation and progression

Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis