Digestive System Diseases Commons^™

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 …

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 …

Many Pediatric Patients With Gastroparesis Do Not Receive Dietary Education, Debra Eseonu, Deepa Dongarwar, Hamisu Salihu, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: Gastroparesis is delayed gastric emptying in the absence of obstruction; dietary modifications are first-line treatment. However, we do not know the factors related to provision of dietary recommendations.

METHODS: We sought to determine how often pediatric patients with gastroparesis receive dietary education (from a gastroenterology provider vs dietitian), the recommendations given, and factors related to these outcomes. We performed a retrospective chart review of children 2- to 18-years-old managed by pediatric gastroenterology providers at our institution. Patient demographics and clinical data, dietary advice given (if any), and dietitian consultation (if any), practice location, and prokinetic use were captured. An …

Actionable Solutions To Achieve Health Equity In Chronic Liver Disease, Patricia D Jones, Jennifer C Lai, Jasmohan S Bajaj, Fasiha Kanwal

Faculty, Staff and Students Publications

There are well-described racial and ethnic disparities in the burden of chronic liver diseases. Hispanic persons are at highest risk for developing nonalcoholic fatty liver disease, the fastest growing cause of liver disease. Hepatitis B disproportionately affects persons of Asian or African descent. The highest rates of hepatitis C occur in American Indian and Alaskan Native populations. In addition to disparities in disease burden, there are also marked racial and ethnic disparities in access to treatments, including liver transplantation. Disparities also exist by gender and geography, especially in alcohol-related liver disease. To achieve health equity, we must address the root …

Closure Of Refractory Gastrocutaneous Fistula With Endoscopically Guided Percutaneous Suturing With The Use Of Miniature Biopsy Forceps, Rogelio Garcia, Juan D Gomez Cifuentes, Fuad Aloor, Tara Keihanian, Marvin Ryou, Wasif M Abidi

Faculty, Staff and Students Publications

A PEG tube is an ideal option for enteral nutrition in patients with impaired swallowing or for nutrition optimization. After PEG tube removal, the tract usually closes spontaneously. However, persistent gastrocutaneous fistula (GCF) is a rare but well-known adverse event of long-term PEG tube use.¹ Despite the evolution of endoscopic techniques over the last decade, such as over-the-scope clips (OTSCs), endoscopic suturing, and biosynthetic glue plaque, the management of GCF remains challenging.2, 3, 4, 5, 6 Although endoscopic suturing results in full-thickness closure of the gastric wall, persistent leakage from the cutaneous site may …

The Predictive Performance Of Contemporary Guideline Recommendations For Helicobacter Pylori Testing In A United States Population, Theresa Nguyen Wenker, Frederick B Peng, Ikenna Emelogu, Niharika Mallepally, Fasiha Kanwal, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: The Houston Consensus Conference and American College of Gastroenterology (ACG) have recommended Helicobacter pylori screening in United States populations with specific risk factors. However, the performance of these guidelines in clinical practice is not known.

METHODS: We identified consecutive patients undergoing upper endoscopy with gastric biopsies for any indication in a safety-net hospital in Houston, TX during January 2015-December 2016. We tested the association between the presence of H pylori (histopathology, stool antigen, urea breath test, immunoglobulin G serology, or prior treatment) and H pylori risk factors using logistic regression models, reported as odds ratios and 95% confidence intervals …

Association Of Chronic Pancreatitis Pain Features With Physical, Mental, And Social Health, Dhiraj Yadav, Robert L Askew, Tonya Palermo, Liang Li, Dana K Andersen, Minxing Chen, William E Fisher, Evan L Fogel, Christopher E Forsmark, Phil A Hart, Mohamed O Othman, Stephen J Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Santhi Swaroop Vege, Yunlong Yang, Jose Serrano, Darwin L Conwell, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities.

METHODS: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants …

Radiological-Histopathological Discordance In Patients Transplanted For Hcc And Its Impact On Post-Transplant Outcomes, Islam B Mohamed, Mohamed Saleh Ismail, Ahmed El Sabagh, Ahmed M Afifi Abdelwahab, Efstathia Polychronopoulou, Yong-Fang Kuo, Manal Hassan, John A Goss, Fasiha Kanwal, Prasun K Jalal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Contrast-enhanced cross-sectional imaging is the cornerstone in the diagnosis, staging, and management of HCC, including eligibility for liver transplantation (LT). Radiological-histopathological discordance may lead to improper staging and may impact patient outcomes. We aimed to assess the radiological-histopathological discordance at the time of LT in HCC patients and its impact on the post-LT outcomes.

METHODS: We analyzed further the effect of 6-month waiting policy on the discordance. Using United Network for Organ Sharing-Organ Procurement and Transplantation Network (UNOS-OPTN) database, we examined the discordance between pre-LT imaging and explant histopathology for all adult HCC patients who received liver …

Using Telemedicine To Facilitate Patient Communication And Treatment Decision-Making Following Multidisciplinary Tumor Board Review For Patients With Hepatocellular Carcinoma, Debra T Choi, Yvonne H Sada, Shubhada Sansgiry, David E Kaplan, Tamar H Taddei, Jason K Aguilar, Michael Strayhorn, Ruben Hernaez, Jessica A Davila

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: A rapid increase in the use of telemedicine for delivering healthcare has occurred since the onset of the Covid-19 pandemic. There is evidence for using telemedicine to facilitate cancer care delivery for patients with hepatocellular carcinoma (HCC). Examining how telemedicine can be used to communicate multidisciplinary tumor board (MTB) recommendations for HCC has not been studied. This study has two specific aims: (1) to evaluate the patient perspective of the MTB review process and identify best strategies for communicating treatment recommendations for HCC and (2) to pilot test a telemedicine intervention following MTB review to assess patient …

Longer Time To Recovery From Acute Kidney Injury Is Associated With Major Adverse Kidney Events In Patients With Cirrhosis, Kavish R Patidar, Mobasshir A Naved, Shaowli Kabir, Ananth Grama, Andrew S Allegretti, Giuseppe Cullaro, Sumeet K Asrani, Astin Worden, Archita P Desai, Marwan S Ghabril, Lauren D Nephew, Eric S Orman

Faculty, Staff and Students Publications

BACKGROUND: In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE).

AIMS: To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis.

METHODS: Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

Rolling Out New Anti-Tuberculosis Drugs Without Diagnostic Capacity, Tara Ness, Le Hong Van, Ilze Petermane, Raquel Duarte, Christoph Lange, Dick Menzies, Daniela Maria Cirillo

Faculty, Staff and Students Publications

Deaths from tuberculosis (TB) reached over 1.6 million in 2021 with 10.6 million people becoming ill. Multidrug-resistant TB, defined as the Mycobacterium tuberculosis organism having resistance to at least isoniazid and rifampicin, represented 3.9% of new TB cases and 18% of previously treated cases. While new drug regimens continue to be developed and introduced to improve treatment of drug-resistant forms of TB, diagnostic capability to identify drug resistance lags woefully behind. While significant mortality benefits exist for these newer drug regimens, implementing them without proper drug resistance diagnostic capacity could lead to development of more drug resistances and exhaust these …

Pediatric Ercp In The Setting Of Acute Pancreatitis: A Secondary Analysis Of An International Multicenter Cohort Study, Carolena Trocchia, Racha Khalaf, Ernest Amankwah, Wenly Ruan, Douglas S Fishman, Bradley A Barth, Quin Y Liu, Matthew Giefer, Kyung Mo Kim, Mercedes Martinez, Luigi Dall'oglio, Filippo Torroni, Paola De Angelis, Simona Faraci, Sam Bitton, Steven L Werlin, Kulwinder Dua, Roberto Gugig, Clifton Huang, Petar Mamula, J Antonio Quiros, Yuhua Zheng, Travis Piester, Amit Grover, Victor L Fox, Michael Wilsey, David M Troendle

Faculty, Staff and Students Publications

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure …

Targets And Study Design For Symptom-Focused Trials Aimed At Patients With Cirrhosis: An Expert Consensus, Arpan A Patel, Elliot B Tapper, Fasiha Kanwal, Christopher D Woodrell, Lissi Hansen, Jennifer C Lai, Shari Rogal, Cara Mcdermott, Mina Rakoski, Nneka N Ufere

Faculty, Staff and Students Publications

BACKGROUND: Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.

METHODS: A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in …

Probiotics And Human Milk Differentially Influence The Gut Microbiome And Nec Incidence In Preterm Pigs, Valeria Melendez Hebib, Diana H Taft, Barbara Stoll, Jinxin Liu, Lee Call, Gregory Guthrie, Nick Jensen, Amy B Hair, David A Mills, Douglas G Burrin

Faculty, Staff and Students Publications

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)—sialylactose (3′SL)—on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 …

Expanding Endoscopic Boundaries: Endoscopic Resection Of Large Appendiceal Orifice Polyps With Endoscopic Mucosal Resection And Endoscopic Submucosal Dissection, Ankur P Patel, Mai A Khalaf, Margarita Riojas-Barrett, Tara Keihanian, Mohamed O Othman

Faculty, Staff and Students Publications

BACKGROUND: Large appendiceal orifice polyps are traditionally treated surgically. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been utilized as alternative resection techniques.

AIM: To evaluate the efficacy and safety of endoscopic resection techniques for the management of large appendiceal orifice polyps.

METHODS: This was a retrospective observational study conducted to assess the feasibility and safety of EMR and ESD for large appendiceal orifice polyps. This project was approved by the Baylor College of Medicine Institutional Review Board. Patients who underwent endoscopic resection of appendiceal orifice polyps ≥ 1 cm from 2015 to 2022 at a tertiary …

The Prevalence And Determinants Of Nafld And Mafld And Their Severity In The Va Primary Care Setting, Aaron P Thrift, Theresa H Nguyen, Codey Pham, Maya Balakrishnan, Fasiha Kanwal, Rohit Loomba, Hao T Duong, David Ramsey, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population.

METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 …

Using Natural Language Processing To Automatically Identify Dysplasia In Pathology Reports For Patients With Barrett's Esophagus, Theresa Nguyen Wenker, Yamini Natarajan, Kadon Caskey, Francisco Novoa, Nabil Mansour, Huy Anh Pham, Jason K Hou, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Identifying dysplasia of Barrett's esophagus (BE) in the electronic medical record (EMR) requires manual abstraction of unstructured data. Natural language processing (NLP) creates structure to unstructured free text. We aimed to develop and validate an NLP algorithm to identify dysplasia in BE patients on histopathology reports with varying report formats in a large integrated EMR system.

METHODS: We randomly selected 600 pathology reports for NLP development and 400 reports for validation from patients with suspected BE in the national Veterans Affairs databases. BE and dysplasia were verified by manual review of the pathology reports. We used NLP …

Exploration Of Associations Among Dietary Tryptophan, Microbiome Composition And Function, And Symptom Severity In Irritable Bowel Syndrome, Anna M Plantinga, Kendra J Kamp, Qinglong Wu, Li Chen, Linda Yoo, Robert L Burr, Kevin C Cain, Daniel Raftery, Fausto Carnevale Neto, Shyam Badu, Sik Yu So, Tor Savidge, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS.

METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and …

Why The Vonoprazan Helicobacter Pylori Therapies In The Us-European Trial Produced Unacceptable Cure Rates, David Y Graham

Faculty, Staff and Students Publications

INTRODUCTION: Helicobacter pylori infects a large percentage of the world's population and is etiologically related to gastric cancer. The U.S. Food and Drug Administration recently approved two 14-day vonoprazan-containing regimens (vonoprazan-amoxicillin with or without clarithromycin) for H. pylori infections in the United States/Europe.

METHODS: We critically reviewed the trial methods to discover why the results were unacceptable low [i.e., no regimen achieved clinically acceptable (≥ 90%) or even conditionally acceptable cure rates (≥ 85%)]. Cure rates with antibiotic susceptible strains were 84.7 for vonoprazan triple therapy, 78.5 for vonoprazan-amoxicillin, and 78.7 for lansoprazole triple therapy, respectively. As was previously shown …

The Predictive Impact Of Dual Somatostatin Receptor/Fluorodeoxyglucose (Fdg) Positron Emission Tomography (Pet) In Metastatic Gastroenteropancreatic Neuroendocrine Tumors (Gep-Nets): Review Of Literature And A Single Institution Experience, Amr Mohamed, Sylvia L Asa, Zhenghong Lee, Sree H Tirumani, Qiubai Li, Norbert Avril, David Bajor, Amit Mahipal, Sakti Chakrabarti, J Eva Selfridge, Arash Kardan

Faculty, Staff and Students Publications

Treatment with radiolabelled somatostatin analogs, a form of peptide receptor radionuclide therapy (PRRT), has changed the management of patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). There is a subgroup of patients who have suboptimal benefit and rapidly progress on PRRT, indicating that accurate prognostic and predictive markers are urgently needed. Currently, most of the literature concentrate on the prognostic impact of the dual positron emission tomography (PET) scan with very few information regarding the predictive value. We report a case series and review the literature to summarizes the predictive value of combined somatostatin receptor (SSTR) and fluorodeoxyglucose (FDG) PET in …

A Precision Environmental Health Approach To Prevention Of Human Disease, Andrea Baccarelli, Dana C Dolinoy, Cheryl Lyn Walker

Faculty, Staff and Students Publications

Human health is determined by the interaction of our environment with the genome, epigenome, and microbiome, which shape the transcriptomic, proteomic, and metabolomic landscape of cells and tissues. Precision environmental health is an emerging field leveraging environmental and system-level ('omic) data to understand underlying environmental causes of disease, identify biomarkers of exposure and response, and develop new prevention and intervention strategies. In this article we provide real-life illustrations of the utility of precision environmental health approaches, identify current challenges in the field, and outline new opportunities to promote health through a precision environmental health framework.

Hepatocyte Srebp Signaling Mediates Clock Communication Within The Liver, Dongyin Guan, Hosung Bae, Dishu Zhou, Ying Chen, Chunjie Jiang, Cam Mong La, Yang Xiao, Kun Zhu, Wenxiang Hu, Trang Minh Trinh, Panpan Liu, Ying Xiong, Bishuang Cai, Cholsoon Jang, Mitchell A Lazar

Faculty, Staff and Students Publications

Rhythmic intraorgan communication coordinates environmental signals and the cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific KO of core components of the molecular clock Rev-erbα and -β (Reverb-hDKO) alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in nonparenchymal cells (NPCs) of the liver. Here, we report that in fatty liver caused by diet-induced obesity (DIO), hepatocyte SREBP cleavage-activating protein (SCAP) was required for Reverb-hDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in liver macrophages (LMs). Integrative analyses of isolated hepatocytes and LMs revealed that SCAP-dependent lipidomic changes in REV-ERB-depleted hepatocytes led to the enhancement of LM metabolic …

The Association Between Caffeine Intake And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Annie Dai, Kristi Hoffman, Anthony A Xu, Shawn Gurwara, Donna L White, Fasiha Kanwal, Albert Jang, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

We examined the association between caffeine and coffee intake and the community composition and structure of colonic microbiota. A total of 34 polyp-free adults donated 97 colonic biopsies. Microbial DNA was sequenced for the 16S rRNA gene V4 region. The amplicon sequence variant was assigned using DADA2 and SILVA. Food consumption was ascertained using a food frequency questionnaire. We compared the relative abundance of taxonomies by low (<82.9 mg) vs. high (≥82.9 mg) caffeine intake and by never or <2 cups vs. 2 cups vs. ≥3 cups coffee intake. False discovery rate-adjusted p values (q values) <0.05 indicated statistical significance. Multivariable negative binomial regression models were used to estimate the incidence rate ratio and its 95% confidence interval of having a non-zero count of certain bacteria by intake level. Higher caffeine and coffee intake was related to higher alpha diversity (Shannon index p < 0.001), higher relative abundance of Faecalibacterium and Alistipes, and lower relative abundance of Erysipelatoclostridium (q values < 0.05). After adjustment of vitamin B2 in multivariate analysis, the significant inverse association between Erysipelatoclostridium count and caffeine intake remained statistically significant. Our preliminary study could not …

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation In Preterm Pigs, Line I Christiansen, Bo Holmqvist, Xiaoyu Pan, Kristine Holgersen, Sandy E H Lindholm, Nicole L Henriksen, Douglas G Burrin, David Ley, Thomas Thymann, Per Torp Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was …

Clinical Implications Of Molecular Drug Resistance Testing For Mycobacterium Tuberculosis: A 2023 Tbnet/Resist-Tb Consensus Statement, José Domínguez, Martin J Boeree, Emmanuelle Cambau, Dumitru Chesov, Francesca Conradie, Vivian Cox, Keertan Dheda, Andrii Dudnyk, Maha R Farhat, Sebastien Gagneux, Martin P Grobusch, Matthias I Gröschel, Lorenzo Guglielmetti, Irina Kontsevaya, Berit Lange, Frank Van Leth, Christian Lienhardt, Anna M Mandalakas, Florian P Maurer, Matthias Merker, Paolo Miotto, Barbara Molina-Moya, Florence Morel, Stefan Niemann, Nicolas Veziris, Andrew Whitelaw, Charles R Horsburgh, Christoph Lange

Faculty, Staff and Students Publications

Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing. Review and the search for evidence included hand-searching journals and searching electronic databases. The panel identified studies that linked mutations in genomic regions of M tuberculosis with treatment outcome data. Implementation of molecular …

Admixture Mapping In African Americans Identifies New Risk Loci For Hcv-Related Cirrhosis, Hyun-Seok Kim, Priya B Shetty, Spiridon Tsavachidis, Jing Dong, Christopher I Amos, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Cirrhosis is the main predisposing condition for hepatocellular carcinoma. Host genetic risk factors have been reported for cirrhosis; however, whether there is a genetic contribution to racial disparities in cirrhosis requires further investigation.

METHODS: We used an affected-only mapping by admixture linkage disequilibrium analysis to characterize the genetic risk of cirrhosis in 227 African American patients with cirrhosis genotyped at 19,804 ancestry-informative marker single nucleotide polymorphisms. We additionally performed analyses stratified by hepatitis C virus (HCV) infection status. To replicate our findings, we conducted a case-control analysis in an external study population (452 cases and 196 controls). …

The Risk Of Hepatocellular Carcinoma In Entecavir Versus Tenofovir Treated Us Cohort With Chronic Hepatitis B Virus, Jennifer R Kramer, Peter A Richardson, Hyunseok Kim, Yao-Chun Hsu, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

The comparative effectiveness of tenofovir (TDF) versus entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (HBV) remains unclear. Data from a retrospective Korean cohort study published by Choi et al. initially suggested lower than expected incidence of HCC in patients on long-term TDF. However, additional studies from Korea did not show a statistically significant difference in HCC incidence rate between TDF and ETV groups, and subsequent studies reported mixed results ranging from no association or a slight advantage for TDF⁴. Most of these studies examined Asian patients from Korea, Taiwan, …

Turmeric-Associated Liver Injury: A Rare Case Of Drug-Induced Liver Injury, David N Smith, Prisca Pungwe, Lauren L Comer, Teminioluwa A Ajayi, Milena G Suarez

Faculty, Staff and Students Publications

Turmeric is popularly used as a naturopathic supplement associated with myriad benefits and has long been generally regarded as safe. However, increasing reports of turmeric-associated liver injury have emerged over recent years. This case presents a female patient without significant past medical history who presents with signs and symptoms of acute hepatitis after consuming a turmeric-containing tea. Her case adds to a growing body of evidence that dosage safety, manufacturing, and pharmacologic delivery practices for turmeric supplements should be investigated.

Longitudinal Changes In Fibrosis Markers Are Associated With Risk Of Cirrhosis And Hepatocellular Carcinoma In Non-Alcoholic Fatty Liver Disease, George Cholankeril, Jennifer R Kramer, Jinna Chu, Xian Yu, Maya Balakrishnan, Liang Li, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Currently, there is no consistent information on the course of fibrosis-4 (FIB-4) score changes in non-alcoholic fatty liver disease (NAFLD) or their association with subsequent risk of cirrhosis and/or hepatocellular carcinoma (HCC). Thus, we aimed to evaluate the association between longitudinal changes in FIB-4 and subsequent risk of HCC and a composite endpoint of cirrhosis and HCC in patients with NAFLD.

METHODS: We conducted a retrospective cohort study of patients with NAFLD seen in 130 Veterans Administration hospitals between 1/1/2004-12/31/2008, with follow-up through to 12/31/2018. We calculated FIB-4 longitudinally and categorized patients based on risk of advanced …