The Use of Palliative Performance Score in Patients with End-Stage Liver Disease

● Palliative Care services are often underutilized in patients with End-Stage Liver Disease (ESLD) and often only initiated at the end of life ● The Palliative Performance Score (PPS) is an important tool used in Palliative Care to assess functional status ● PPS has five functional dimensions: ambulation, activity level and evidence of disease, self-care, oral intake, and level of consciousness ● The aim of this study is to determine if there is a correlation between Model for End-Stage Liver Disease (MELD) score and PPS in ESLD patients ● MELD is used to predict mortality and to prioritize liver transplant allocation in ESLD patientshttps://jdc.jefferson.edu/medposters/1011/thumbnail.jp

Coronary Artery Disease and Nonalcoholic Fatty Liver Disease: Clinical Correlation Using CT Coronary Calcium Scans

Introduction: Nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) have been explored with coronary angiography which showed a link between severe NAFLD and CVD risk. This study’s aim is to determine if CT coronary artery calcium (CAC) scores used to determine CAD severity in asymptomatic populations can help predict presence of NAFLD. Methods: Retrospective cross-sectional study of positive CT CAC scores and liver imaging with either CT, ultrasound, or MRI of the abdomen or CT of the chest. Drinking 7 or 14 drinks per week for a woman or man respectively and chronic viral hepatitis diagnosis were excluding criteria. CT CAC scores and hepatic steatosis were correlated by chi-squared analysis. Age, sex, lipid and liver panels, weight, blood pressure, and hemoglobin A1c were correlated to CAD severity and NAFLD by logistic regression. Results: 134 patients with a median age of 63 years (IQR 57-69), 65% male, BMI 28.5 (IQR 23.9-31.3), and 8% diabetes. CAD severity was not associated with presence of hepatic steatosis (p = 0.36). Multivariate logistic regression showed a link between hepatic steatosis, CAD severity, BMI over 30 (p = 0.02), and diabetes (p = 0.01). There were associations between hepatic steatosis with triglycerides (p = 0.03) and CAD severity with AST (p = 0.02). Discussion: In patients with CAD detected using a positive CAC CT scan, we determined that BMI over 30 and diabetes were markers of increased NAFLD risk. We determined there was no direct relationship between CAD and hepatic steatosis presence

Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes

Acentral tenet of nerve growth factor (NGF) action that is poorly understood is its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is initiated at the nerve terminal and conveyed to the soma. We identified an NGF-induced protein that we termed Pincher (pinocytic chaperone) that mediates endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells, overexpression of Pincher dramatically stimulated NGF-induced endocytosis of TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell surface ruffles. Subsequently, a system of Pincher-containing tubules mediated the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA endosomes with persistent signaling potential

Lit up and left dark: Failures of imagination in urban broadband networks

The design and deployment of urban broadband infrastructures inscribe particular imaginations of Internet access onto city streets. The different manifestations and locations of these networks, their uses, and access points often expose material excesses of urban broadband networks, as well as failures of Internet service providers, urban planners, and public officials to imagine the diverse ways that people incorporate Internet connection into their everyday lives. We approach the study of urban broadband networks through the juxtaposition of invisible networks that are buried under the streets and have always been “turned off” (dark fiber) versus hypervisible that are “turned on” and prominently displayed on city streets (LinkNYC). In our analysis of these two case studies, we critique themes of visibility and invisibility as indexes of power and access. Our findings are meant to provide a critical analysis of urban technology policy as well as theories of infrastructure, visibility, and access

Comprehensive Review of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease

Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk. We also discuss the emerging and complex biochemical relationship between NAFLD and its common comorbid conditions, and how they coalesce to increase CVD risk. With NAFLD\u27s rising prevalence and deleterious effects on the cardiovascular system, a complete understanding of the disease must be undertaken, as well as effective strategies to prevent and treat its common comorbid conditions

Locative Media and Sociability:Using Location-Based Social Networks to Coordinate Everyday Life

Foursquare was a mobile social networking application that enabled people to share location with friends in the form of “check-ins.” The visualization of surrounding known social connections as well as unknown others has the potential to impact how people coordinate social encounters and forge new social ties. While many studies have explored mobile phones and sociability, there is a lack of empirical research examining location-based social network’s (LSBNs) from a sociability perspective. Drawing on a dataset of original qualitative research with a range of Foursquare users, the paper examines the application in the context of social coordination and sociability in three ways. First, the paper explores if Foursquare is used to organize certain social encounters, and if so, why. Second, the paper examines the visualization of surrounding social connections and whether this leads to “serendipitous encounters.” Lastly, the paper examines whether the use of Foursquare can produce new social relationships

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals

The impact of currently licensed therapies on viral and immune responses in Chronic Hepatitis B: considerations for future novel therapeutics.

Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussedWellcome Trust Clinical Research Training Fellowship (107389/Z/15/Z)NIHR Academic Clinical LectureshipBarts Charity Project Grants (723/1795 and MGU/0406NIHR Research for patient benefit award (PB‐PG‐0614‐34087) to PTF