Progression to cirrhosis is similar among all ages in nonalcoholic fatty liver disease, but liver-related events increase with age.

Background: NAFLD is increasingly common among young people. Whether NAFLD carries a more benign course in younger adults is not known. We aimed to characterize genetic and metabolic risk factors for NAFLD and their effects on disease progression across age groups.

A Drosophila Su(H) model of Adams-Oliver Syndrome reveals cofactor titration as a mechanism underlying developmental defects.

Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant.

Systematic review: radiomics for the diagnosis and prognosis of hepatocellular carcinoma.

Background: Advances in imaging technology have the potential to transform the early diagnosis and treatment of hepatocellular carcinoma (HCC) through quantitative image analysis. Computational "radiomic" techniques extract biomarker information from images which can be used to improve diagnosis and predict tumour biology.

Aims: To perform a systematic review on radiomic features in HCC diagnosis and prognosis, with a focus on reporting metrics and methodologic standardisation.

Neutrophil-to-Lymphocyte Ratio Predicts High-Risk Explant Features and Waitlist Survival But Is Not Independently Associated With Recurrence or Survival Following Liver Transplantation for Hepatocellular Carcinoma.

We assessed the prognostic significance and the clinical stability of the neutrophil-to-lymphocyte ratio (NLR) before liver transplantation (LT) in a large cohort of patients with hepatocellular carcinoma (HCC) from a region with a long waitlist time. A high preoperative NLR ≥5 has been reported to predict poor outcomes following LT for HCC, and the NLR has been incorporated into several prognostic models. We evaluated 758 patients with HCC with Model for End-Stage Liver Disease exceptions and listed for LT from 2002 to 2015 at a single LT center, of which 505 underwent LT and 253 dropped out before LT.

Social Support Does Not Modify the Risk of Readmission for Patients with Decompensated Cirrhosis.

Background: Patients with decompensated cirrhosis are at high risk of frequent hospitalizations. Whether the level of perceived social support impacts this risk is unknown. We sought to determine the relationship between social support and burden of hospitalization in patients with decompensated cirrhosis.

Accuracy of medical billing data against the electronic health record in the measurement of colorectal cancer screening rates.

Objective: Medical billing data are an attractive source of secondary analysis because of their ease of use and potential to answer population-health questions with statistical power. Although these datasets have known susceptibilities to biases, the degree to which they can distort the assessment of quality measures such as colorectal cancer screening rates are not widely appreciated, nor are their causes and possible solutions.

Methods: Using a billing code database derived from our institution's electronic health records, we estimated the colorectal cancer screening rate of average-risk patients aged 50-74 years seen in primary care or gastroenterology clinic in 2016-2017.

Gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression.

Background: Preclinical evidence suggests that modulation of the gut microbiome could represent a new therapeutic target in nonalcoholic fatty liver disease (NAFLD).

Objectives: The aim of this study was to evaluate the most current evidence for liver-specific and metabolic effects of microbiome-targeted therapies (MTTs) in persons with NAFLD.

Methods: We searched multiple electronic databases for randomized controlled trials (RCTs) published from January 1, 2005 to December 1, 2018 that enrolled persons with NAFLD who received MTT rather than placebo or usual care.

Correction to: Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature.

This paper was inadvertently published with open access; the authors have requested the copyright revert to the society. It has been re-published with appropriate licensing.

Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature.

Ehlers-Danlos syndrome refers to a spectrum of connective tissue disorders typically caused by mutations in genes responsible for the synthesis of collagen. Patients with Ehlers-Danlos syndrome often exhibit hyperflexibility of joints, increased skin elasticity, and tissue fragility. Vascular Ehlers-Danlos (vEDS) is a subtype of Ehlers-Danlos syndrome with a predilection to involve blood vessels.

Spontaneous Bacterial Peritonitis due to in Cirrhosis.

species colonize the human gastrointestinal tract and are rarely pathogenic. We present a case involving a cirrhotic patient who presented with sepsis and was found to have peritoneal cultures demonstrating as the sole pathogen concerning for spontaneous bacterial peritonitis. Treatment was achieved with high-dose penicillin and clindamycin but the patient developed hepatorenal syndrome and died from acute renal failure.

Defective K-Ras oncoproteins overcome impaired effector activation to initiate leukemia in vivo.

Reversing the aberrant biochemical output of oncogenic Ras proteins is one of the great challenges in cancer therapeutics; however, it is uncertain which Ras effectors are required for tumor initiation and maintenance. To address this question, we expressed oncogenic K-Ras(D12) proteins with "second site" amino acid substitutions that impair PI3 kinase/Akt or Raf/MEK/ERK activation in bone marrow cells and transplanted them into recipient mice. In spite of attenuated signaling properties, defective K-Ras oncoproteins initiated aggressive clonal T-lineage acute lymphoblastic leukemia (T-ALL).

Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice.

Children with neurofibromatosis type 1 (NF1) are predisposed to juvenile myelomonocytic leukemia (JMML), an aggressive myeloproliferative neoplasm (MPN) that is refractory to conventional chemotherapy. Conditional inactivation of the Nf1 tumor suppressor in hematopoietic cells of mice causes a progressive MPN that accurately models JMML and chronic myelomonocytic leukemia (CMML). We characterized the effects of Nf1 loss on immature hematopoietic populations and investigated treatment with the MEK inhibitor PD0325901 (hereafter called 901).

Hematopoiesis and leukemogenesis in mice expressing oncogenic NrasG12D from the endogenous locus.

NRAS is frequently mutated in hematologic malignancies. We generated Mx1-Cre, Lox-STOP-Lox (LSL)-Nras(G12D) mice to comprehensively analyze the phenotypic, cellular, and biochemical consequences of endogenous oncogenic Nras expression in hematopoietic cells. Here we show that Mx1-Cre, LSL-Nras(G12D) mice develop an indolent myeloproliferative disorder but ultimately die of a diverse spectrum of hematologic cancers.