Gastroenterology Commons^™

Association Between Microbiome And The Development Of Adverse Posttraumatic Neuropsychiatric Sequelae After Traumatic Stress Exposure, Abigail L. Zeamer, Marie-Claire Salive, Xinming An, Francesca L. Beaudoin, Stacey L. House, Jennifer S. Stevens, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Sarah D. Linnstaedt, Scott L. Rauch, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Erica Harris, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Ronald C. Kessler, Karestan C. Koenen, Samuel A. Mclean, Vanni Bucci, John P. Haran

Einstein Health Papers

Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA …

Advancements In Understanding And Treating Nafld: A Comprehensive Review Of Metabolic-Associated Fatty Liver Disease And Emerging Therapies, Jacob Beiriger, Kashyap Chauhan, Adnan Khan, Taha Shahzad, Natali Salinas, Peter Zhang, Sarah Chen, Anh Nguyen, Brian Yan, John Bruckbauer, Dina Halegoua-De Marzio

Department of Medicine Faculty Papers

This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article …

Acute Hepatic Porphyrias: Recommendations For Diagnosis And Management With Real-World Examples, Akshata Moghe, Amy Dickey, Angelika Erwin, Rebecca K. Leaf, Alan O'Brien, John G. Quigley, Manish Thapar, Karl E. Anderson

Division of Gastroenterology and Hepatology Faculty Papers

Acute hepatic porphyria (AHP) is a group of four rare inherited diseases, each resulting from a deficiency in a distinct enzyme in the heme biosynthetic pathway. Characterized by acute neurovisceral symptoms that may mimic other medical and psychiatric conditions, lack of recognition of the disease often leads to a delay in diagnosis and initiation of effective treatment. Biochemical testing for pathway intermediates that accumulate when the disease is active forms the basis for screening and establishing a diagnosis. Subsequent genetic analysis identifies the pathogenic variant, supporting screening of family members and genetic counseling. Management of AHP involves avoidance of known …

Perforated Pre-Pyloric Ulcer In The Gastric Remnant Over A Decade After Roux-En-Y Gastric Bypass: A Case Report, Bianca Marquez, Emmanuel Luciano, Ryan Cohen, Christina Maser, Matthew Hubbard

Einstein Health Papers

INTRODUCTION AND IMPORTANCE: Roux-en-Y gastric bypass (RYGB) is one of the two most common weight loss surgeries. Surgical emergencies after gastric bypass can be complicated by devastating events that are often difficult to diagnose and manage. Perforated ulcers are a very rare complication after a RYGB.

CASE PRESENTATION: In this report, the diagnosis and surgical management of a 59-year-old immunosuppressed male patient who presented with late perforation of a pre-pyloric ulcer in the gastric remnant after RYGB is presented. The perforation was repaired transversely in a running horizontal mattress fashion and patched with a piece of well-vascularized omentum.

CLINICAL DISCUSSION: …

The Efficacy Of Fecal Microbiota Transplantation (Fmt) On Symptom Reduction In Patients With Irritable Bowel Syndrome (Ibs), Carly Liberatore

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

• IBS is a functional gastrointestinal tract disorder that affects 5-10% of the population.¹
• Symptom severity ranges from mild to severe interference with daily life.¹
• Current treatments are highly ineffective and focus on relieving symptoms rather than solving the root problem, gut dysbiosis.^{5, 6}
• Aim: To determine if FMT significantly reduces symptom severity in IBS patients

A Hypothetical New Challenging Use For Indocyanine Green Fluorescence During Laparoscopic Appendectomy: A Mini-Series Of Our Experience And Literary Review, Noemi Zorzetti, Augusto Lauro, Manuela Cuoghi, Marco La Gatta, Ignazio R. Marino, Salvatore Sorrenti, Vito D'Andrea, Andrea Mingoli, Giuseppe Giovanni Navarra

Department of Surgery Faculty Papers

Laparoscopic appendectomy (LA) is a well-standardized surgical procedure, but there are still controversies about the different devices to be used for the appendiceal stump closure and the related postoperative complications. Indocyanine green (ICG) fluorescence angiography (FA) has already been shown to be helpful in elective and emergency surgery, providing intraoperative information on tissue and organ perfusion, thus guiding the surgical decisions and the technical strategies. According to these two aspects, we report a mini-series of the first five patients affected by gangrenous and flegmonous acute appendicitis intraoperatively evaluated with ICG-FA during LA. The patients were admitted to the Emergency Department …

Per Oral Endoscopic Myotomy In Pregnancy, Julie Gomez, Laura Felder, Divya Chalikonda, Alexander Schlachterman, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To report the first successful full-term delivery following Per Oral Endoscopic Myotomy (POEM) performed during pregnancy.

METHODS/BACKGROUND: Achalasia is an esophageal motility disorder characterized by dysphagia, regurgitation, reflux, recurrent vomiting, and weight loss. Achalasia in pregnancy can affect nutritional status of the mother, and subsequently, the child, increasing morbidity and creating potential pregnancy complications. POEM is a novel endoscopic procedure which involves cutting the lower esophageal sphincter to allow food to pass, and is considered a safe and effective management option for achalasia in non-pregnant individuals.

RESULTS: We discuss the case of a patient with achalasia and a prior …

The Long Game: A Functional Cure Is Possible With Nucleoside Analogues And The Tincture Of Time, Nicholas Noverati, Vivian Yan, Jay Jun, Dina Halegoua-De Marzio, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B is still prevalent globally. Many patients are treated for many years with nucleos(t)ide analogues to prevent the virus from actively replicating. However, although it typically requires consecutive treatment for more than 10 years, patients can achieve a functional cure from this virus. This case series presents details of functional cures in patients who received varying nucleos(t)ide therapies for an average of 15.3 years before losses of hepatitis B surface antigen and viral load were observed. It is imperative to understand that abbreviating therapy once a functional cure is achieved may be a possibility in treating patients in …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …

A Novel Endoscopic Ultrasound-Guided Transluminal Anchor Device, Abhishek Agnihotri, Alexander Schlachterman

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Safety And Indications For Endoscopic Retrograde Cholangiopancreatography In Liver Transplant Patients: An Analysis Of The United States’ National Inpatient Sample Database, Zahid Ijaz Tarar, Umer Farooq, Mustafa Gandhi, Muhammad Usman Zafar, Saad Saleem, Faisal Kamal

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is performed to treat biliary complications after a liver transplantation; however, the previously available literature on the safety of ERCP in liver transplant patients is limited. We aimed to study the safety of ERCP in liver transplant patients.

METHODS: We used a National Inpatient Sample database from 2016-2019 to identify patients who underwent ERCP and had a history of a liver transplantation, using the international classification of diseases, 10

RESULTS: Liver transplant patients who underwent ERCP had a higher rate of post-ERCP pancreatitis and bleeding compared to the general adult population (11.39% vs. 9.19%, 0.83% …

Persistently Elevated Hbv Viral-Host Junction Dna In Urine As A Biomarker For Hepatocellular Carcinoma Minimum Residual Disease And Recurrence: A Pilot Study, Selena Y Lin, Dina Halegoua-De Marzio, Peter Block, Yu-Lan Kao, Jesse M. Civan, Fwu-Shan Shieh, Wei Song, Hie-Won Hann, Ying-Hsiu Su

Department of Medicine Faculty Papers

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV–HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, …

Chronicles Of Hbv And The Road To Hbv Cure, Rukaiya Bashir Hamidu, Richard R. Hann, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to …

Comprehensive Review Of Acute Pancreatitis Pain Syndrome, Jacob Beiriger, Adnan Khan, Brian Yan, Heather Ross, Makala Wang, Michael Carducci, Natali Salinas, Salil Chowdhury, Ryan Erwin, Sarah Chen, Alexis Gerber

Jefferson Hospital Staff Papers and Presentations

Pancreatitis is a condition that causes inflammation in the pancreas, an organ located behind the stomach. This condition often presents as neuropathic, inflammatory, and/or visceral pain. Acute pancreatitis is typically characterized by sudden and severe abdominal pain, often in the upper right part of the abdomen. The pain from pancreatitis can be caused by different mechanisms, such as abnormal activation of pancreatic zymogens or NF-κB mediated inflammation in the pancreas. The treatment of pancreatitis depends on its type, severity, and underlying cause. Hospitalization and medications are typically necessary, while in others, surgery may be required. Proper management of pancreatitis is …

A Review Of The Cardiovascular Safety Of Prucalopride In Patients With Chronic Idiopathic Constipation, Jan Tack, Katayoun Derakhchan, André Gabriel, William Spalding, Brian Terreri, Ashraf Youssef, Bahij Kreidieh, Peter R. Kowey, Mena Boules

Division of Cardiology Faculty Papers

Prokinetic agents, specifically 5-hydroxytryptamine type 4 (5-HT 4 ) receptor agonists, have been shown to provide relief in chronic idiopathic constipation (CIC). The first-generation 5-HT 4 agonists were initially withdrawn from use owing to associations with serious cardiovascular (CV) events. This review summarizes CV safety data for prucalopride, a high-affinity 5-HT 4 agonist approved in the United States in 2018 for adults with CIC. No significant effects of prucalopride on CV safety were observed in animal models or early-phase clinical studies, including a thorough QT study at therapeutic (2 mg) or supratherapeutic (10 mg) doses. Among 1,750 patients with CIC …

Acute Systemic Infection-Associated Russell Body Gastroesophagitis: A Case Report And Literature Review, Elizaveta Flerova, Susan Inniss, Nneamaka Nwaoduah, Richard P. Denicola, Jialing Huang

Division of Gastroenterology and Hepatology Faculty Papers

Russell body esophagitis/gastritis (RBG) is a rare gastrointestinal inflammatory condition characterized by accumulation of plasma cells containing dense eosinophilic cytoplasmic inclusions, i.e., Russell bodies. Herein, we report a case of RBG in a patient with a systemic inflammation background. A 61-year-old female presented with oral infection. Upper gastrointestinal endoscopy revealed patchy salmon-colored esophageal mucosa proximally to the gastroesophageal junction, suggestive of “Barrett’s esophagus”. Histologic examination of the biopsy tissue from the lower esophagus showed diffuse lymphoplasmacytic infiltration with abundant admixed enlarged plasma cells (Mott cells) containing bright eosinophilic, round, dense, homogenous inclusions (Russell bodies) in cytoplasm. Immunohistochemical study demonstrated membranous …

Intestinal Neuropod Cell Gucy2c Regulates Visceral Pain, Joshua R. Barton, Annie K. Londregran, Tyler D. Alexander, Ariana A. Entezari, Shely Bar-Ad, Lan Cheng, Angelo C. Lepore, Adam E. Snook, Manuel Covarrubias, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP(cGMP), which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we revealed that intestinal GUCY2C was selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2Chi neuropod cells associated with cocultured dorsal root ganglia neurons and induced hyperexcitability, reducing the rheobase and increasing the resulting …

Unrecognized Functional Dyspepsia Among Those With Refractory Chronic Constipation: Analysis Of A Tertiary Cohort, Taylor Boyd, Mary Paz, Imama Ahmad, Fatima Rao, Ahmad Samad, Isabelle Garcia-Fischer, Casey Silvernale, Helen Burton Murray, Kyle Staller

Student Papers, Posters & Projects

BACKGROUND AND AIMS: Patients with functional constipation (FC) are frequently dissatisfied with current treatment options which may be related to persistent, unaddressed symptoms. We hypothesized that refractory FC may actually represent functional dyspepsia (FD) overlap. Among adults presenting with refractory FC, we sought to (1) identify the prevalence of concurrent FD and (2) identify the symptoms and presentations most frequently associated with concurrent FD and FC.

METHODS: We assembled a retrospective cohort of 308 patients sequentially presenting to a tertiary neurogastroenterology clinic for evaluation of refractory FC, defined as having failed first-line therapy. Using Rome IV criteria, trained raters identified …

Mendelian Randomization Analysis Reveals A Complex Genetic Interplay Among Atopic Dermatitis, Asthma, And Gastroesophageal Reflux Disease, Kwangmi Ahn, Raymond B. Penn, Satish Rattan, Reynold A. Panettieri, Benjamin F. Voight, Steven S. An

Division of Gastroenterology and Hepatology Faculty Papers

RATIONALE: Gastroesophageal reflux disease (GERD) is commonly associated with atopic disorders, but cause-effect relationships remain unclear.

OBJECTIVES: We applied Mendelian randomization (MR) analysis to explore whether GERD is causally related to atopic disorders of the lung (asthma) and/or skin (atopic dermatitis).

METHODS: We conducted two-sample bidirectional MR to infer the magnitude and direction of causality between asthma and GERD, using summary statistics from the largest genome-wide association studies (GWAS) conducted on asthma (N_cases=56,167) and GERD (N_cases=71,522). Additionally, we generated instrumental variables (IVs) for atopic dermatitis (AD) from the latest population-level GWAS meta-analysis (N_cases=22,474) and …

Alcoholic Vs. Nonalcoholic Steatohepatitis: Vascular Branching Heterogeneity On Magnetic Resonance Imaging As A Diagnostic Marker, Daniel Garrido, Nicholas Noverati, Justin Robbins, Jaydev K. Dave, Haresh V. Naringrekar, Donald Mitchell, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Background and aims: Distinguishing alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) with biopsy alone is often difficult without a reliable clinical context. A novel finding on liver imaging, perivascular branching heterogeneity, has shown promise in distinguishing between these chronic liver diseases. Our study investigated the role of this finding on imaging to differentiate between ASH and NASH. The aim of this study was to determine the utility and reproducibility of this novel radiographic marker to help distinguish ASH from NASH.

Methods: This was a retrospective cohort study conducted between 2016 and 2020 in patients with both liver biopsy-confirmed steatohepatitis/chronic hepatitis …

"Keep Your Chin Up, And Keep Eating": Perceptions Of Barriers And Facilitators To Healthful Dietary Behaviors Among Individuals With Gastrointestinal Cancer And Caregivers, Brandy-Joe Milliron, Cynthia Klobodu, Jonathan Deutsch, Karon Martyn, Dan Dychtwald, Emily Riahi, Shawn Carro, Taylor Hisek, Natalie Darcy, Ann C. Klassen

Kimmel Cancer Center Faculty Papers

BACKGROUND: This study explored perceptions of barriers and facilitators to healthful dietary behaviors among patients with gastrointestinal (GI) cancer and their caregivers, including caregiver preparedness, patient and caregiver self-efficacy for symptom management, and other environmental, social, and familial factors that may serve as barriers and facilitators to healthful eating.

METHODS: Using a concurrent mixed methods cross-sectional study design, individuals with GI cancer receiving outpatient chemotherapy and their caregivers completed surveys, dietary assessments, and interviews. Caregiving preparedness, self-efficacy for symptom management, and dietary intake were assessed using validated instruments. Dietary quality was measured using the Healthy Eating Index (HEI)-2020. In-depth interviews …

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.