Medical Specialties Commons^™

Myocardial Infarction With Nonobstructive Coronary Arteries In New-Onset Inflammatory Bowel Disease, Benjamin B. Claxton, George Sun, Ritu Nahar, Christopher Henry

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Treatment Of Severe Swallowing Dysfunction In Systemic Sclerosis With Ivig: Role Of Antimuscarinic Antibodies, Fabian A Mendoza, Anthony J. Dimarino, Sidney Cohen, Christopher Adkins, Shady Abdelbaki, Satish Rattan, Christopher Cao, Susie Denuna-Rivera, Sergio A. Jimenez

Division of Gastroenterology and Hepatology Faculty Papers

Oropharyngeal and esophageal dysmotility can cause serious clinical complications such as aspiration pneumonia, cachexia, and sarcopenia, with a resulting increase in mortality and disability. The current standard of care for the treatment of SSc-associated swallowing dysfunction is mainly supportive, although severe cases are usually refractory to conventional management. Recent studies have shown that the abnormal production of functional autoantibodies such as anti-cholinergic muscarinic receptor III antibodies may participate in the pathogenesis of SSc-associated gastrointestinal dysmotility and may provide a novel target for therapeutic intervention. We describe two patients with severe and rapid onset of SSc-associated severe swallowing dysfunction and esophageal …

Accuracy Of Noninvasive Diagnostic Tests For The Detection Of Significant And Advanced Fibrosis Stages In Nonalcoholic Fatty Liver Disease: A Systematic Literature Review Of The Us Studies, Dhaval Gosalia, Vlad Ratziu, Filip Stanicic, Djurdja Vukicevic, Vladimir Zah, Nadege Gunn, Dina Halegoua-De Marzio, Tram Tran

Department of Medicine Faculty Papers

Background: The purpose of this systematic literature review (SLR) was to evaluate the accuracy of noninvasive diagnostic tools in detecting significant or advanced (F2/F3) fibrosis among patients with nonalcoholic fatty liver (NAFL) in the US healthcare context.

Methods: The SLR was conducted in PubMed and Web of Science, with an additional hand search of public domains and citations, in line with the PRISMA statement. The study included US-based original research on diagnostic test sensitivity, specificity and accuracy.

Results: Twenty studies were included in qualitative evidence synthesis. Imaging techniques with the highest diagnostic accuracy in F2/F3 detection and differentiation were magnetic …

The Socioeconomic Impact On Presentation And Clinical Course Of Celiac Disease, Christopher Cao, Md, Peter Block, Md, Madeline Russell, Md, Justin Robbins, Md, Anthony J. Dimarino, Md, Stephanie Moleski

Division of Gastroenterology and Hepatology Posters

Introduction

• Celiac Disease (CD) is a chronic autoimmune condition primarily affecting the small intestine.
• CD is triggered by ingestion of gluten and the only effective treatment for CD involves strict and lifelong elimination of dietary gluten.
• Compliance with the gluten free diet (GFD) relies on purchasing gluten-free foods. Studies have shown the cost of a GFD to be from 76% to 518% more expensive than gluten containing counterparts. Because of this, the economic burden that CD patients face may be substantial, placing these patients at high risk for dietary neglect.
• Financial limitation aside, GFD availability also varies by differing neighborhoods, …

Disease Burden In Patients With Acute Hepatic Porphyria: Experience From The Phase 3 Envision Study, Bruce Wang, Paolo Ventura, Kei-Ichiro Takase, Manish Thapar, David Cassiman, Ilja Kubisch, Shangbin Liu, Marianne T Sweetser, Manisha Balwani

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Acute hepatic porphyria (AHP) is a family of four rare genetic diseases, each involving deficiency in a hepatic heme biosynthetic enzyme. Resultant overproduction of the neurotoxic intermediates δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) leads to disabling acute neurovisceral attacks and progressive neuropathy. We evaluated the AHP disease burden in patients aged ≥ 12 years in a post hoc analysis of the Phase 3, randomized, double-blind, placebo-controlled ENVISION trial of givosiran (NCT03338816), an RNA interference (RNAi) therapeutic that targets the enzyme ALAS1 to decrease ALA and PBG production. We analyzed baseline AHP severity via chronic symptoms between attacks, comorbidities, concomitant …

Functional, Diagnostic And Therapeutic Aspects Of Bile, Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Bile is a unique body fluid synthesized in our liver. Enterohepatic circulation preserves bile in our body through its efficient synthesis, transport, absorption, and reuptake. Bile is the main excretory route for bile salts, bilirubin, and potentially harmful exogenous lipophilic substances. The primary way of eliminating cholesterol is bile. Although bile has many organic and inorganic contents, bile acid is the most physiologically active component. Bile acids have a multitude of critical physiologic functions in our body. These include emulsification of dietary fat, absorption of fat and fat-soluble vitamins, maintaining glucose, lipid, and energy homeostasis, sustenance of intestinal epithelial integrity …

Disease Burden And Management Of Crigler-Najjar Syndrome: Report Of A World Registry, Sem J Aronson, Norman Junge, Mediha Trabelsi, Wided Kelmemi, Aurelie Hubert, Karlla W Brigatti, Michael D. Fox, Robert J De Knegt, Johanna C Escher, Virginia M Ginocchio, Raffaele Iorio, Yan Zhu, Figen Özçay, Fakher Rahim, Mortada H F El-Shabrawi, Eyal Shteyer, Angelo Di Giorgio, Lorenzo D'Antiga, Federico Mingozzi, Nicola Brunetti-Pierri, Kevin A Strauss, Philippe Labrune, Ridha Mrad, Ulrich Baumann, Ulrich Beuers, Piter J Bosma

Department of Pediatrics Faculty Papers

Background and Aims Crigler-Najjar syndrome (CNS) is a disorder of bilirubin conjugation leading to brain damage and death without treatment. Although cohort studies of limited size have been published, uncertainty about outcome, co-morbidities, occurence of liver fibrosis and treatment outcome remains. With this worldwide cohort study, we aim to add substantial knowledge to the previously published data.

Methods Anonymized retrospective data of CNS patients were collected in a web-based registry platform.

Results Clinical data of 221 CNS patients (46% female, severe phenotype n = 209) were collected. At the time of analysis, 59 CNS patients were deceased. Mean serum total …

Alpha-Fetoprotein (Afp) And Afp-L3 Is Most Useful In Detection Of Recurrence Of Hepatocellular Carcinoma In Patients After Tumor Ablation And With Low Afp Level, Madison Force, Grace Park, Divya Chalikonda, Christopher G. Roth, Micah Cohen, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been …

Hur Plays A Role In Double-Strand Break Repair In Pancreatic Cancer Cells And Regulates Functional Brca1-Associated-Ring-Domain-1(Bard1) Isoforms, Aditi Jain, Matthew Mccoy, Carolyn Coats, Samantha Z Brown, Sankar Addya, Carl Pelz, Rosalie C Sears, Charles Yeo, Jonathan R Brody

Department of Surgery Faculty Papers

Human Antigen R (HuR/ELAVL1) is known to regulate stability of mRNAs involved in pancreatic ductal adenocarcinoma (PDAC) cell survival. Although several HuR targets are established, it is likely that many remain currently unknown. Here, we identified BARD1 mRNA as a novel target of HuR. Silencing HuR caused a >70% decrease in homologous recombination repair (HRR) efficiency as measured by the double-strand break repair (pDR-GFP reporter) assay. HuR-bound mRNAs extracted from RNP-immunoprecipitation and probed on a microarray, revealed a subset of HRR genes as putative HuR targets, including the BRCA1-Associated-Ring-Domain-1 (BARD1) (p < 0.005). BARD1 genetic alterations are infrequent in PDAC, and its context-dependent upregulation is poorly understood. Genetic silencing (siRNA and CRISPR knock-out) and pharmacological targeting of HuR inhibited both full length (FL) BARD1 and its functional isoforms (α, δ, Φ). Silencing BARD1 sensitized cells to olaparib and oxaliplatin; caused G2-M cell cycle arrest; and increased DNA-damage while decreasing HRR efficiency in cells. Exogenous overexpression of BARD1 in HuR-deficient cells partially rescued the HRR dysfunction, independent of an HuR pro-oncogenic function. Collectively, our findings demonstrate for the first time that BARD1 is a bona fide HuR target, which serves as an important regulatory point of the transient DNA-repair response in PDAC cells.

Hepatitis B Virus-Associated Hepatocellular Carcinoma And Chronic Stress, Nicholas Noverati, Rukaiya Bashir, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host's immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host's defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, …

Longitudinal Analysis Of The Impact Of Oral Contraceptive Use On The Gut Microbiome, Xinwei Hua, Yueming Cao, David M Morgan, Kaia Miller, Samantha M Chin, Danielle Bellavance, Hamed Khalili

Department of Medicine Faculty Papers

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding …