Noninvasive Assessment of Acute Graft-Versus-Host Disease of the Gastrointestinal Tract After Allogeneic Hemopoietic Stem Cell Transplantation Using 18F-FDG PET.

Acute graft-versus-host disease of the gastrointestinal tract (acute GIT-GVHD) often complicates allogeneic hemopoietic stem cell transplantation (AHSCT). 18F-FDG PET/CT is known to detect active inflammation and may be a useful noninvasive test for acute GIT-GVHD. The objective of this study was to evaluate the diagnostic utility of 18F-FDG PET/CT to noninvasively assess patients with clinically suspected acute GIT-GVHD. Fifty-one AHSCT patients with clinically suspected acute GIT-GVHD prospectively underwent 18F-FDG PET/CT scanning followed by upper and lower GIT endoscopy within 7 d. Endoscopic biopsies of 4 upper GIT and 4 colonic segments were obtained for histology to compare with corresponding quantitative segmental 18F-FDG PET/CT SUVmax Receiver-operating-characteristic curve (ROC) analysis was performed to determine predictive capacity of 18F-FDG PET/CT SUVmax for acute GIT-GVHD. A separate qualitative visual 18F-FDG PET/CT analysis was also performed for comparison. Results: Twenty-three of 51 (45.1%) patients had biopsy-confirmed acute GIT-GVHD, with 19 of 23 (82.6%) having upper GIT and 22 of 22 (100%) colonic involvement. One of 23 patients did not undergo a colonoscopy. GVHD involved the entire colon contiguously in 21 of 22 patients. For quantitative analysis, histology from 4 upper GIT and 4 colonic segments were compared with 18F-FDG PET/CT SUVmax Colonic segments positive for GVHD had a higher SUVmax (4.1 [95% CI, 3.6-4.5]) than did normal colonic segments (2.3 [1.9-2.7], P = 0.006). No difference was demonstrated in upper GIT segments. Quantitative 18F-FDG PET/CT yielded a 69% sensitivity, 57% specificity, 73% negative predictive value, and 59% positive predictive value for the detection of GVHD compared with 70%, 76%, 76%, and 68%, respectively, for qualitative analysis. Conclusion: 18F-FDG PET is a useful noninvasive diagnostic test for acute GIT-GVHD, which when present always involves the colon and usually in its entirety, suggesting colonic biopsy obtained by sigmoidoscopy is adequate for histologic confirmation when acute GIT-GVHD is suspected. Of note, 18F-FDG PET cannot distinguish acute GIT-GVHD from non-GVHD inflammatory changes in the colon.

A multi-site, nurse-coordinated hepatitis C model of care in primary care and community services in Melbourne, Australia.

BACKGROUND: Hepatitis C virus (HCV) treatment through primary care and community-based services will be a critical component of HCV elimination. We evaluated a nurse-coordinated programme providing care across eight sites and analysed progression through the HCV care cascade. METHODS: People-accessing services from six primary care clinics, a homeless crisis accommodation provider and a mental health service were directly referred to nurses or engaged by nurses during regular clinic visits. Nurses supported HCV testing, treatment and follow-up. The prescription was provided by affiliated clinicians. Logistic regression was used to examine factors associated with treatment commencement and sustained virological response (SVR) testing. RESULTS: Of 640 people referred to and/or engaged by the nurses from January 2017 to July 2019, 518 had an HCV RNA test of whom 381 (74%) were HCV RNA positive. Treatment was commenced by 281 (74%) people of whom 161 had an SVR test, 157 (97.5%) were cured. Opioid agonist therapy was associated with treatment commencement (aOR 2.68, 95% CI 1.48-4.88). People who were homeless/unstably housed were less likely to commence treatment (aOR 0.45, 95% CI 0.23-0.87). Treatment prescription from a specialist (aOR 2.39, 95% CI 1.20-4.74) and recent injection drug use (<6 months) (aOR 2.15, 95% CI 1.07-4.31) was associated with SVR testing. CONCLUSION: A nurse-coordinated model of care led to high levels of HCV treatment uptake and cure amongst people attending primary care and community services. More tailored models of care may be beneficial for people who are homeless or have unstable housing. These results support primary care and community-based hepatitis C treatment.

Viscoelastic Tests as Point-of-Care Tests in the Assessment and Management of Bleeding and Thrombosis in Liver Disease.

Viscoelastic point-of-care (VET POC) tests provide a global assessment of hemostasis and have an increasing role in the management of bleeding and blood component delivery across several clinical settings. VET POC tests have a rapid turnaround time, provide a better overall picture of hemostasis, predict bleeding more accurately than conventional coagulation tests, and reduce blood component usage and health care costs. Despite commonly having abnormal conventional coagulation tests, most patients with chronic liver disease have a "rebalanced" hemostasis. However, this hemostatic balance is delicate and these patients are predisposed to both bleeding and thromboembolic events. Over recent years, VET POC tests have been increasingly studied for their potential as better functional tests of hemostasis in liver disease patients. This review provides a background on the most common VET POC tests (thromboelastography and rotational thromboelastometry) and discusses the current evidence for these tests in the prediction and management of bleeding and thrombosis in patients with chronic liver disease, and in liver resection and transplant. With the recent publication of several randomized controlled trials, there is growing evidence that VET POC tests may be used to improve bleeding risk assessment and reduce blood product use in liver disease patients outside of the transplant setting. However, consensus is still lacking regarding the VET POC tests' thresholds that should be used to trigger blood product transfusion. VET POC tests also show promise in predicting thrombosis in patients with liver disease, but further research is needed before they can be used to guide anticoagulant therapy.

Nonalcoholic fatty liver disease: current concepts, epidemiology and management strategies.

Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the world. It involves a spectrum of conditions from hepatic steatosis to nonalcoholic steatohepatitis and liver fibrosis, and is a major cause of cirrhosis and hepatocellular carcinoma. It is defined by presence of steatosis in 5% of hepatocytes or more in the absence of other causes of fatty liver. The metabolic syndrome is the major known risk factor for NAFLD. Dietary contributors such as high fructose intake and coffee consumption appear to increase and decrease the risk of disease respectively, but these links are unclear. Genetic associations have also been identified. The estimated prevalence of the disease varies according to diagnostic method and population demographics. It appears to be a major issue in Europe with population studies showing up to 50% of the individuals are affected while in the USA one in three adults are estimated to have NAFLD. Laboratory investigations and ultrasound are typically first-line investigations. Fibrosis may be assessed noninvasively through transient elastography and biomarkers but liver biopsy remains the gold standard to quantify hepatic damage. Associated comorbidities include cardiovascular disease and chronic kidney disease. Weight loss, dietary changes and exercise are recommended in management. Medications should be considered to manage underlying risk factors including insulin resistance. Surgical options include bariatric procedures and liver transplantation. The combination of rising prevalence and significant potential complications warrant further research into NAFLD, particularly in areas with research gaps including Eastern Europe.

Longitudinal study of health, disease and access to care in rural Victoria: the Crossroads-II study: methods.

BACKGROUND: High quality, contemporary data regarding patterns of chronic disease is essential for planning by health services, policy makers and local governments, but surprisingly scarce, including in rural Australia. This dearth of data occurs despite the recognition that rural Australians live with high rates of ill health, poor health behaviours and restricted access to health services. Crossroads-II is set in the Goulburn Valley, a rural region of Victoria, Australia 100-300 km north of metropolitan Melbourne. It is primarily an irrigated agricultural area. The aim of the study is to identify changes in the prevalence of key chronic health conditions including the extent of undiagnosed and undermanaged disease, and association with access to care, over a 15 year period. METHODS/DESIGN: This study is a 15 year follow up from the 2000-2003 Crossroads-I study (2376 households participated). Crossroads-II includes a similar face to face household survey of 3600 randomly selected households across four towns of sizes 6300 to 49,800 (50% sampled in the larger town with the remainder sampled equally from the three smaller towns). Self-reported health, health behaviour and health service usage information is verified and supplemented in a nested sub-study of 900 randomly selected adult participants in 'clinics' involving a range of additional questionnaires and biophysical measurements. The study is expected to run from October 2016 to December 2018. DISCUSSION: Besides providing epidemiological and health service utilisation information relating to different diseases and their risk factors in towns of different sizes, the results will be used to develop a composite measure of health service access. The importance of access to health services will be investigated by assessing the correlation of this measure with rates of undiagnosed and undermanaged disease at the mesh block level. Results will be shared with partner organisations to inform service planning and interventions to improve health outcomes for local people.

Impact of heart failure and changes to volume status on liver stiffness: non-invasive assessment using transient elastography.

AIM: The impact of cardiac dysfunction on the liver is known as cardiac hepatopathy. In certain instances this can result in significant hepatic fibrosis or cirrhosis. The validity of non-invasive tools to assess hepatic fibrosis, such as FibroScan(®) which measures liver stiffness (LSM), has not been established in this setting. We examined the impact of cardiac dysfunction on LSM using FibroScan(®) and the influence of volume changes on LSM. METHODS AND RESULTS: A prospective, cross-sectional study examined the use of FibroScan(®) in subjects with left-sided heart failure (LHF, n = 32), right-sided heart failure (RHF, n = 9), and acute decompensated heart failure (ADHF, n = 8). The impact of volume changes upon LSM was further examined in the ADHF group (pre- and post-diuresis) and in a haemodialysis group (HD, n = 12), pre- and post-ultrafiltration on dialysis. Compared with healthy controls [n = 55, LSM = median 4.4 (25th percentile 3.6, 75th percentile 5.1) kPa], LSM was increased in all the cardiac dysfunction subgroups [LHF, 4.7 (4.0, 8.7) kPa, P = 0.04; RHF, 9.7 (5.0, 10.8) kPa, P < 0.001; ADHF, 11.2 (6.7, 14.3) kPa, P < 0.001]. Alteration in volume status via diuresis did not change the baseline LSM in ADHF [11.2 (6.7, 14.3) to 9.5 (7.3, 21.6) kPa, P > 0.05] with mean diuresis 5051 ± 1585 mL, or ultrafiltration in HD [6.0 (3.6, 5.1) vs. 5.7 (4.8, 7.0) kPa, P > 0.05] with mean diuresis 1962 ± 233 mL. CONCLUSION: Our findings support the concept of increased LSM in the cardiac failure population. LSM was not altered to a statistically significant level with acute volume changes.

The long summer: pre-wintering temperatures affect metabolic expenditure and winter survival in a solitary bee.

The impact of climate change on insect populations depends on specific life cycle traits and physiological adaptations. The solitary bee Osmia lignaria winters as a pre-emergent adult, and requires a period of cold temperature for winter diapause completion. It is a univoltine species, and diapause induction does not depend on photoperiod. To understand the potential effects of longer summers on O. lignaria populations, we exposed individuals to three treatments simulating early, mid and late winter arrivals, and measured respiration rates, metabolic expenditure, weight loss, fat body depletion, lipid levels and winter mortality. The early-winter treatment disrupted diapause development, but had no apparent negative effects on fitness. In contrast, late-winter bees had a greater energetic expenditure (1.5-fold), weight (1.4-fold) and lipid (2-fold) loss, greater fat body depletion, and a 19% increase in mortality compared to mid-winter bees. We also monitored adult eclosion and arrival of winter temperatures under natural conditions in four years. We found a positive correlation between mean degree-day accumulation during pre-wintering (a measure of asynchrony between adult eclosion and winter arrival) and yearly winter mortality. Individually, bees experiencing greater degree-day accumulations exhibited reduced post-winter longevity. Timing of adult eclosion in O. lignaria is dependent on the duration of the prepupal period, which occurs in mid-summer, is also diapause-mediated, and is longer in populations from southerly latitudes. In a global warming scenario, we expect long summer diapause phenotypes to replace short summer diapause phenotypes, effectively maintaining short pre-wintering periods in spite of delayed winter arrivals.