Digestive System Diseases Commons^™

Tuberculosis Incidence In Foreign-Born People Residing In European Countries In 2020, Anca Vasiliu, Niklas Köhler, Ekkehardt Altpeter, Tinna Rán Ægisdóttir, Marina Amerali, Wouter Arrazola De Oñate, Ágnes Bakos, Stefania D'Amato, Daniela Maria Cirillo, Reinout Van Crevel, Edita Davidaviciene, Irène Demuth, Jose Domínguez, Raquel Duarte, Gunar Günther, Jean-Paul Guthmann, Sophia Hatzianastasiou, Louise Hedevang Holm, Zaida Herrador, Urška Hribar, Conny Huberty, Elmira Ibraim, Sarah Jackson, Mogens Jensenius, Kamilla Sigridur Josefsdottir, Anders Koch, Maria Korzeniewska-Kosela, Liga Kuksa, Heinke Kunst, Christian Lienhardt, Beatrice Mahler, Mateja Janković Makek, Inge Muylle, Johan Normark, Analita Pace-Asciak, Goranka Petrović, Despo Pieridou, Giulia Russo, Olena Rzhepishevska, Helmut J F Salzer, Marta Sá Marques, Daniela Schmid, Ivan Solovic, Mariya Sukholytka, Petra Svetina, Mariya Tyufekchieva, Tuula Vasankari, Piret Viiklepp, Kersti Villand, Jiri Wallenfels, Stefan Wesolowski, Anna-Maria Mandalakas, Leonardo Martinez, Dominik Zenner, Christoph Lange, Tbnet

Faculty, Staff and Students Publications

Background

European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.

Aim

We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.

Methods

The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries …

Validation Of A Pre-Endoscopy Risk Score For Predicting The Presence Of Gastric Intestinal Metaplasia In A Us Population, Mimi C Tan, Ahana Sen, Eugene Kligman, Mohamed O Othman, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Surveillance of gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. Our purpose was to externally validate a predictive model for endoscopic GIM previously developed in a veteran population in a second U.S.

METHODS: We previously developed a pre-endoscopy risk model for detection of GIM using 423 GIM cases and 1796 control subjects from the Houston Veterans Affairs Hospital. The model included sex, age, race/ethnicity, smoking, and Helicobacter pylori infection with an area under the receiver-operating characteristic curve (AUROC) of .73 for GIM and .82 for extensive GIM. We validated this model in a second …

Bioimpedance Analysis Predicts The Etiology Of Cirrhosis In A Prospective Cohort Study, Hashem B El-Serag, Ghida Akhdar, Aaron P Thrift, Michelle Luster, Saira Khaderi, Abeer Alsarraj, Hao Duong, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND: Obesity is associated with an increased risk of developing cirrhosis. However, body mass index (BMI) and waist-to-hip ratio (WHR) may not be indicative of body composition parameters that predispose to cirrhosis. Bioimpedance analysis (BIA) is a noninvasive cost-efficient method for more detailed estimation of body composition.

METHODS: We examined patients with cirrhosis who underwent BIA as part of enrollment into a prospective cohort study. We examined the correlation between BIA variables, BMI, and WHR. We performed sex-adjusted and race-adjusted and race-specific multivariable logistic regression analyses to examine the association between anthropometric variables and risk factors [NAFLD, alcohol-associated liver disease …

A Novel Prediction Model Of The Risk Of Pancreatic Cancer Among Diabetes Patients Using Multiple Clinical Data And Machine Learning, Shih-Min Chen, Phan Thanh Phuc, Phung-Anh Nguyen, Whitney Burton, Shwu-Jiuan Lin, Weei-Chin Lin, Christine Y Lu, Min-Huei Hsu, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic cancer is associated with poor prognosis. Considering the increased global incidence of diabetes cases and that individuals with diabetes are considered a high-risk subpopulation for pancreatic cancer, it is critical to detect the risk of pancreatic cancer within populations of person living = with diabetes. This study aimed to develop a novel prediction model for pancreatic cancer risk among patients with diabetes, using = a real-world database containing clinical features and employing numerous artificial intelligent approach algorithms.

METHODS: This retrospective observational study analyzed data on patients with Type 2 diabetes from a multisite Taiwanese EMR database between 2009 …

Setd2 Safeguards The Genome Against Isochromosome Formation, Frank M Mason, Emily S Kounlavong, Anteneh T Tebeje, Rashmi Dahiya, Tiffany Guess, Abid Khan, Logan Vlach, Stephen R Norris, Courtney A Lovejoy, Ruhee Dere, Brian D Strahl, Ryoma Ohi, Peter Ly, Cheryl Lyn Walker, W Kimryn Rathmell

Faculty, Staff and Students Publications

Isochromosomes are mirror-imaged chromosomes with simultaneous duplication and deletion of genetic material which may contain two centromeres to create isodicentric chromosomes. Although isochromosomes commonly occur in cancer and developmental disorders and promote genome instability, mechanisms that prevent isochromosomes are not well understood. We show here that the tumor suppressor and methyltransferase SETD2 is essential to prevent these errors. Using cellular and cytogenetic approaches, we demonstrate that loss of SETD2 or its epigenetic mark, histone H3 lysine 36 trimethylation (H3K36me3), results in the formation of isochromosomes as well as isodicentric and acentric chromosomes. These defects arise during DNA replication and are …

Inhibition Of Trap1 Accelerates The Dna Damage Response, Activation Of The Heat Shock Response And Metabolic Reprogramming In Colon Cancer Cells, Nobel Bhasin, Prerna Dabral, Lakmini Senavirathna, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

BACKGROUND: Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. The tumor microenvironment plays a significant role in CRC development, progression and metastasis. Oxidative stress in the colon is a major etiological factor impacting tumor progression. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial member of the heat shock protein 90 (HSP90) family that is involved in modulating apoptosis in colon cancer cells under oxidative stress. We undertook this study to provide mechanistic insight into the role of TRAP1 under oxidative stress in colon cells.

METHODS: We first assessed the The Cancer Genome Atlas …

A Rare Cause Of Diarrhea: Intestinal Spirochetosis In An Hiv-Positive Patient., Lacey Falgout, Shilpa Kailas, Supraja Sridhar, Nisha Loganantharaj

School of Medicine Faculty Publications

Intestinal spirochetosis (IS) is a rare gastrointestinal infection with vague presenting symptoms. Diagnosis is confirmed histopathologically. Risk factors include homosexuality and HIV. Antibiotic treatment with metronidazole usually leads to resolution of symptoms. We present the case of a 56-year-old HIV-positive man with chronic, watery diarrhea who was diagnosed with IS. This case highlights the importance of considering IS in the differential in HIV-positive patients with nonspecific gastrointestinal symptoms after more common etiologies have been ruled out.

Prevalence Of Fibromyalgia And Chronic Fatigue Syndrome Among Individuals With Irritable Bowel Syndrome: An Analysis Of United States National Inpatient Sample Database, Zahid Ijaz Tarar, Umer Farooq, Ahmad Nawaz, Mustafa Gandhi, Yezaz A Ghouri, Asmeen Bhatt, Brooks D Cash

Faculty, Staff and Student Publications

Background and Aim: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with other somatic disorders. We studied the prevalence and predictors of fibromyalgia and chronic fatigue syndrome (CFS) in IBS patients. Methods: We used the National Inpatient Sample and included hospitalization of individuals with IBS, using ICD-10 codes, from 2016–2019. The prevalence and predictors of fibromyalgia and CFS in IBS patients were studied. Univariate and multivariate patient- and hospital-level regression models were used to calculate the adjusted odds of fibromyalgia and CFS in the IBS patient population. Results: Of 1,256,325 patients with an ICD-10 code of IBS included …

A Blood-Based Metabolomic Signature Predictive Of Risk For Pancreatic Cancer, Ehsan Irajizad, Ana Kenney, Tiffany Tang, Jody Vykoukal, Ranran Wu, Eunice Murage, Jennifer B Dennison, Marta Sans, James P Long, Maureen Loftus, John A Chabot, Michael D Kluger, Fay Kastrinos, Lauren Brais, Ana Babic, Kunal Jajoo, Linda S Lee, Thomas E Clancy, Kimmie Ng, Andrea Bullock, Jeanine M Genkinger, Anirban Maitra, Kim-Anh Do, Bin Yu, Brian M Wolpin, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the …

Tgfβ Signaling Links Early Life Endocrine-Disrupting Chemicals Exposure To Suppression Of Nucleotide Excision Repair In Rat Myometrial Stem Cells, Maria Victoria Bariani, Yan-Hong Cui, Mohamed Ali, Tao Bai, Sandra L Grimm, Cristian Coarfa, Cheryl L Walker, Yu-Ying He, Qiwei Yang, Ayman Al-Hendy

Faculty, Staff and Students Publications

Environmental exposure to endocrine-disrupting chemicals (EDCs) is linked to the development of uterine fibroids (UFs) in women. UFs, non-cancerous tumors, are thought to originate from abnormal myometrial stem cells (MMSCs). Defective DNA repair capacity may contribute to the emergence of mutations that promote tumor growth. The multifunctional cytokine TGFβ1 is associated with UF progression and DNA damage repair pathways. To investigate the impact of EDC exposure on TGFβ1 and nucleotide excision repair (NER) pathways, we isolated MMSCs from 5-month-old Eker rats exposed neonatally to diethylstilbestrol (DES), an EDC, or to vehicle (VEH). EDC-MMSCs exhibited overactivated TGFβ1 signaling and reduced mRNA …

Braf V600e/Ras Mutations And Lynch Syndrome In Patients With Msi-H/Dmmr Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors, Raphael Colle, Sara Lonardi, Marine Cachanado, Michael J Overman, Elena Elez, Marwan Fakih, Francesca Corti, Priya Jayachandran, Magali Svrcek, Antoine Dardenne, Baptiste Cervantes, Alex Duval, Romain Cohen, Filippo Pietrantonio, Thierry André

Faculty, Staff and Student Publications

BACKGROUND: We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome (LS).

PATIENTS AND METHODS: Patients were defined as LS-linked if germline mutation was detected and as sporadic if loss of MLH1/PMS2 expression with BRAFV600E mutation and/or MLH1 promoter hypermethylation, or biallelic somatic MMR genes mutations were found. Progression-free survival (PFS) and overall survival (OS) were adjusted on prognostic modifiers selected on unadjusted analysis (P < .2) if limited number of events.

RESULTS: Of 466 included patients, 305 (65.4%) and 161 (34.5%) received, respectively, anti-PD1 alone and anti-PD1+anti-CTLA4 …

Clinically Conserved Genomic Subtypes Of Gastric Adenocarcinoma, Yun Seong Jeong, Young-Gyu Eun, Sung Hwan Lee, Sang-Hee Kang, Sun Young Yim, Eui Hyun Kim, Joo Kyung Noh, Bo Hwa Sohn, Seon Rang Woo, Moonkyoo Kong, Deok Hwa Nam, Hee-Jin Jang, Hyun-Sung Lee, Shumei Song, Sang Cheul Oh, Jeeyun Lee, Jaffer A Ajani, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately …

Anesthesia Care Provider Sedation Versus Conscious Sedation For Endoscopic Ultrasound-Guided Tissue Acquisition: A Retrospective Cohort Study, Sneha Shaha, Yinglin Gao, Jiahao Peng, Kendrick Che, John J Kim, Wasseem Skef

Faculty, Staff and Students Publications

BACKGROUND/AIMS: We aimed to study the effects of sedation on endoscopic ultrasound-guided tissue acquisition.

METHODS: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound-guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS).

RESULTS: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234-1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in …

Low Pitch Significantly Reduces Helical Artifacts In Abdominal Ct, Moiz Ahmad, Peng Sun, Christine B Peterson, Marcus R Anderson, Xinming Liu, Ajaykumar C Morani, Corey T Jensen

Faculty, Staff and Student Publications

Purpose: High helical pitch scanning minimizes scan times in CT imaging, and thus also minimizes motion artifact and mis-synchronization with contrast bolus. However, high pitch produces helical artifacts that may adversely affect diagnostic image quality. This study aims to determine the severity and incidence of helical artifacts in abdominal CT imaging and their relation to the helical pitch scan parameter.

Methods: To obtain a dataset with varying pitch values, we used CT exam data both internal and external to our center. A cohort of 59 consecutive adult patients receiving an abdomen CT examination at our center with an accompanying prior …

Stromal-Derived Nrg1 Enables Oncogenic Kras Bypass In Pancreas Cancer, Jincheng Han, Jiaqian Xu, Yonghong Liu, Shaoheng Liang, Kyle A Labella, Deepavali Chakravarti, Denise J Spring, Yan Xia, Ronald A Depinho

Faculty, Staff and Student Publications

Activating KRAS mutations (KRAS*) in pancreatic ductal adenocarcinoma (PDAC) drive anabolic metabolism and support tumor maintenance. KRAS* inhibitors show initial antitumor activity followed by recurrence due to cancer cell-intrinsic and immune-mediated paracrine mechanisms. Here, we explored the potential role of cancer-associated fibroblasts (CAFs) in enabling KRAS* bypass and identified CAF-derived NRG1 activation of cancer cell ERBB2 and ERBB3 receptor tyrosine kinases as a mechanism by which KRAS*-independent growth is supported. Genetic extinction or pharmacological inhibition of KRAS* resulted in up-regulation of ERBB2 and ERBB3 expression in human and murine models, which prompted cancer cell utilization of CAF-derived NRG1 as a …

Exome Sequencing Implicates Dgkz , Esrra , And Gxylt1 For Modulating Granuloma Formation In Crohn Disease, R Alan Harris, Allyson H Bush, Todd N Eagar, Justin Qian, Michael P Greenwood, Antone R Opekun, Robert Baldassano, Stephen L Guthery, Joshua D Noe, Anthony Otley, Joel R Rosh, Subra Kugathasan, Richard Kellermayer

Faculty, Staff and Students Publications

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases. PLINK (a tool set for whole-genome association and population-based linkage analyses) analysis was used to identify single nucleotide polymorphisms (SNPs) differentiating between groups, and subgroup allele frequencies were also compared to a public genomic database (gnomAD). The Combined Annotation Dependent Depletion scoring tool was used …

Age Differences In Core Symptoms And Symptom Relationships In Patients With Irritable Bowel Syndrome: A Network Analysis, Pei-Lin Yang, Kendra J Kamp, Robert L Burr, Hsin-Yi Jean Tang, Adrian Dobra, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age.

METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify …

Fibrosis Induced By Resident Macrophages Has Divergent Roles In Pancreas Inflammatory Injury And Pdac, John M Baer, Chong Zuo, Liang-I Kang, Angela Alarcon De La Lastra, Nicholas C Borcherding, Brett L Knolhoff, Savannah J Bogner, Yu Zhu, Liping Yang, Jennifer Laurent, Mark A Lewis, Nan Zhang, Ki-Wook Kim, Ryan C Fields, Wayne M Yokoyama, Jason C Mills, Li Ding, Gwendalyn J Randolph, David G Denardo

Faculty, Staff and Students Publications

Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation …

Acute Esophageal Necrosis And Duodenal Disease In The Setting Of Recently Initiated Chemotherapy, Kulveer Dabb, Ryan Jansen Van Rensburg, Heba Yusuf, Daniel Klein, Alexander D. Lake, Mohamed Kaif

HCA Healthcare Journal of Medicine

Introduction

Acute esophageal necrosis (AEN), commonly referred to as “black esophagus” or Gurvits syndrome, is a rare condition characterized by diffuse black mucosa in the distal esophagus. Most often, the patient is an older male with multiple comorbidities, presenting with upper gastrointestinal bleeding. The exact pathogenesis is unclear, but it is often thought to be secondary to acute vascular hypo-perfusion or ischemia of the esophageal mucosa in critically ill patients with certain secondary comorbid conditions such as renal insufficiency, diabetes mellitus, dyslipidemia, coronary artery disease, malnourishment, alcohol abuse, or association with an underlying malignancy.

Case Presentation

We present a case …

Developing Electronic Clinical Quality Measures To Assess The Cancer Diagnostic Process, Daniel R Murphy, Andrew J Zimolzak, Divvy K Upadhyay, Li Wei, Preeti Jolly, Alexis Offner, Dean F Sittig, Saritha Korukonda, Riyaa Murugaesh Rekha, Hardeep Singh

Faculty, Staff and Student Publications

OBJECTIVE: Measures of diagnostic performance in cancer are underdeveloped. Electronic clinical quality measures (eCQMs) to assess quality of cancer diagnosis could help quantify and improve diagnostic performance.

MATERIALS AND METHODS: We developed 2 eCQMs to assess diagnostic evaluation of red-flag clinical findings for colorectal (CRC; based on abnormal stool-based cancer screening tests or labs suggestive of iron deficiency anemia) and lung (abnormal chest imaging) cancer. The 2 eCQMs quantified rates of red-flag follow-up in CRC and lung cancer using electronic health record data repositories at 2 large healthcare systems. Each measure used clinical data to identify abnormal results, evidence of …

Dimethyl Sulfoxide Inhibits Bile Acid Synthesis In Healthy Mice But Does Not Protect Mice From Bile-Acid-Induced Liver Damage, Xi Chen, Huiqiao Li, Yu'e Liu, Jing Qi, Bingning Dong, Shixia Huang, Shangang Zhao, Yi Zhu

Faculty, Staff and Students Publications

Bile acids serve a vital function in lipid digestion and absorption; however, their accumulation can precipitate liver damage. In our study, we probed the effects of dimethyl sulfoxide (DMSO) on bile acid synthesis and the ensuing liver damage in mice induced by bile acids. Our findings indicate that DMSO efficaciously curbs bile acid synthesis by inhibiting key enzymes involved in the biosynthetic pathway, both in cultured primary hepatocytes and in vivo. Contrarily, we observed that DMSO treatment did not confer protection against bile-acid-induced liver damage in two distinct mouse models: one induced by a 0.1% DDC diet, leading to bile …

Spatial Transcriptomics Of Intraductal Papillary Mucinous Neoplasms Of The Pancreas Identifies Nkx6-2 As A Driver Of Gastric Differentiation And Indolent Biological Potential, Marta Sans, Yuki Makino, Jimin Min, Kimal I Rajapakshe, Michele Yip-Schneider, C Max Schmidt, Mark W Hurd, Jared K Burks, Javier A Gomez, Fredrik I Thege, Johannes F Fahrmann, Robert A Wolff, Michael P Kim, Paola A Guerrero, Anirban Maitra

Faculty, Staff and Student Publications

Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbor a gastric foveolar-type epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of IPMNs, followed by orthogonal and cross species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric …

Heterozygous Midnolin Knockout Attenuates Severity Of Nonalcoholic Fatty Liver Disease In Mice Fed A Western-Style Diet High In Fat, Cholesterol, And Fructose, Soo-Mi Kweon, Jose Irimia-Dominguez, Gayeoun Kim, Patrick T Fueger, Kinji Asahina, Keith K Lai, Daniela S Allende, Quincy R Lai, Chih-Hong Lou, Walter M Tsark, Ju Dong Yang, Dominic S Ng, Ju-Seog Lee, Patrick Tso, Wendong Huang, Keane K Y Lai

Faculty, Staff and Student Publications

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first …

Reduction In Racial And Ethnic Disparity In Survival Following Liver Transplant For Hepatocellular Carcinoma In The Direct-Acting Antiviral Era, Anjiya Shaikh, Karthik Goli, Tzu-Hao Lee, Nicole E Rich, Jihane N Benhammou, Stephanie Keeling, Donghee Kim, Aijaz Ahmed, John Goss, Abbas Rana, Amit G Singal, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC.

METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, …

Interim Results From An Ongoing, Open-Label, Single-Arm Trial Of Odevixibat In Progressive Familial Intrahepatic Cholestasis, Richard J Thompson, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Angelo Di Giorgio, Özlem Durmaz, Emmanuel Gonzalès, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H J Houwen, Binita M Kamath, Saul J Karpen, Florence Lacaille, Alain Lachaux, Elke Lainka, Kathleen M Loomes, Cara L Mack, Jan P Mattsson, Patrick Mckiernan, Quanhong Ni, Hasan Özen, Sanjay R Rajwal, Bertrand Roquelaure, Eyal Shteyer, Etienne Sokal, Ronald J Sokol, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Wendy L Van Der Woerd, Henkjan J Verkade, Jennifer M Vittorio, Terese Wallefors, Natalie Warholic, Qifeng Yu, Patrick Horn, Lise Kjems

Faculty, Staff and Students Publications

BACKGROUND & AIMS: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis.

METHODS: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up …

Food For Thought: Remission Of Perianal Pediatric Crohn's Disease On Specific Carbohydrate Diet Monotherapy, David Simon, Kalyani Patel, Prakash Masand, Richard Kellermayer

Faculty, Staff and Students Publications

There is growing interest among patients about the specific carbohydrate diet (SCD) as a treatment for Crohn's disease. In the meantime, deep remission in patients using SCD as their sole treatment has not been documented. We report a case with perianal and ileocolonic Crohn's disease in whom SCD monotherapy successfully induced and maintained not only clinical, but also endoscopic, radiographic and histologic (ie, deep mucosal remission) remission as well.

Pediatric Acute Liver Failure Secondary To Autoimmune Hepatitis In An Infant With Thrombocytopenia-Absent Radius (Tar) Syndrome: A Case Report, Rebecca Mercedes, Kalyani Patel, Henry Shiau, Krupa R Mysore, Wenly Ruan, Daniel H Leung, Mary Elizabeth M Tessier, Dana Cerminara, Sarah Nicholas, Kelby Fuller, Marielle Faraone, N Thao N Galvan, John Goss, Anna M Banc-Husu

Faculty, Staff and Students Publications

Thrombocytopenia absent radius (TAR) syndrome is a rare genetic disorder that has been associated with food protein-induced allergic proctocolitis and transient leukemoid reactions, among other manifestations. There has been no prior reports of its association with autoimmune disease, more specifically, autoimmune hepatitis (AIH) or the development of pediatric acute liver failure (PALF). We present a case of an 8-month-old infant with TAR syndrome who presented with PALF, secondary to AIH with elevated liver-kidney microsomal antibody (>1:2560). She received a liver transplant and had a very complicated postoperative course including severe T-cell-mediated rejection, infection, biliary stricture, persistently elevated liver-kidney microsomal …

Safety And Efficacy Of Underwater Versus Conventional Endoscopic Mucosal Resection For Colorectal Polyps: Systematic Review And Meta-Analysis Of Rcts, Saurabh Chandan, Jay Bapaye, Shahab R Khan, Babu P Mohan, Daryl Ramai, Dushyant S Dahiya, Mohammad Bilal, Peter V Draganov, Mohamed O Othman, Joaquin Rodriguez Sánchez, Gursimran S Kochhar

Faculty, Staff and Students Publications

Background and study aims Conventional endoscopic mucosal resection (C-EMR) is limited by low en-bloc resection rates, especially for large (> 20 mm) lesions. Underwater EMR (U-EMR) has emerged as an alternative for colorectal polyps and is being shown to improve en-bloc resection rates. We conducted a systematic review and meta-analysis comparing the two techniques.

Methods Multiple databases were searched through November 2022 for randomized controlled trials (RCTs) comparing outcomes of U-EMR and C-EMR for colorectal polyps. Meta-analysis was performed to determine pooled proportions and relative risks (RRs) of R0 and en-bloc resection, polyp recurrence, resection time, and adverse events.

Results …

Cooperative Activation Of Pdk1 And Akt By Mapk4 Enhances Cancer Growth And Resistance To Therapy, Dong Han, Wei Wang, Julie Heejin Jeon, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang

Faculty, Staff and Students Publications

Phosphoinositide-dependent kinase-1 (PDK1) is a master kinase of the protein A, G, and C (AGC) family kinases that play important roles in regulating cancer cell proliferation, survival, and metabolism. Besides phosphorylating/activating AKT at the cell membrane in a PI3K-dependent manner, PDK1 also exhibits constitutive activity on many other AGC kinases for tumor-promoting activity. In the latter case, PDK1 protein levels dominate its activity. We previously reported that MAPK4, an atypical MAPK, can PI3K-independently promote AKT activation and tumor growth. Here, using triple-negative breast cancer (TNBC) cell models, we demonstrate that MAPK4 can also enhance PDK1 protein synthesis, thus phosphorylate/activate PDK1 …

Interrater Reliability Of Functional Lumen Imaging Probe Panometry And High-Resolution Manometry For The Assessment Of Esophageal Motility Disorders, Joan W Chen, Abraham Khan, Reena V Chokshi, John O Clarke, Ronnie Fass, Jose M Garza, Milli Gupta, C Prakash Gyawali, Anand S Jain, Philip Katz, Vani Konda, Adriana Lazarescu, Kristle L Lynch, Felice Schnoll-Sussman, Stuart J Spechler, Marcelo F Vela, Rena Yadlapati, Jacob M Schauer, Peter J Kahrilas, John E Pandolfino, Dustin A Carlson

Faculty, Staff and Students Publications

INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations.

METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard.

RESULTS: Fifteen raters completed the HRM and FLIP studies. An …