Digestive System Diseases Commons^™

Methylation Quantitative Trait Loci Are Largely Consistent Across Disease States In Crohn’S Disease, Suresh Venkateswaran, Hari K Somineni, Varun Kilaru, Seyma Katrinli, Jarod Prince, David T Okou, Jeffrey S Hyams, Lee A Denson, Richard Kellermayer, Greg Gibson, David J Cutler, Alicia K Smith, Subra Kugathasan, Karen N Conneely

Faculty, Staff and Students Publications

Recently, we identified 1,189 CpG sites whose DNA methylation level in blood associated with Crohn's disease. Here, we examined associations between DNA methylation and genetic variants to identify methylation quantitative trait loci across disease states in (1) 402 blood samples from 164 newly diagnosed pediatric Crohn's disease patients taken at 2 time points (diagnosis and follow-up), and 74 non-inflammatory bowel disease controls, (2) 780 blood samples from a non-Crohn's disease adult population, and (3) 40 ileal biopsies (17 Crohn's disease cases and 23 non-inflammatory bowel disease controls) from group (1). Genome-wide DNAm profiling and genotyping were performed using the Illumina …

Exposure To Per- And Polyfluoroalkyl Substances And Markers Of Liver Injury: A Systematic Review And Meta-Analysis, Elizabeth Costello, Sarah Rock, Nikos Stratakis, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Dora Cserbik, Todd Jenkins, Stavra A Xanthakos, Rohit Kohli, Stephanie Sisley, Vasilis Vasiliou, Michele A La Merrill, Hugo Rosen, David V Conti, Rob Mcconnell, Leda Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver.

OBJECTIVE: The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies.

METHODS: PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For …

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …

Comparison Of Endoscopic Ultrasound-Directed Transgastric Endoscopic Retrograde Cholangiopancreatography Outcomes Using Various Technical Approaches, Firas Bahdi, Rollin George, Kavea Paneerselvam, Dang Nguyen, Wasif M Abidi, Mohamed O Othman, Isaac Raijman

Faculty, Staff and Students Publications

Background and study aims  Roux-en-Y gastric bypass presents an anatomic challenge for patients needing ERCP. EUS-directed transgastric ERCP (EDGE) offers high clinical success but carries considerable risk of adverse events (AEs) with no standardized technical approach. In our study, we review the safety and efficacy of our various EDGE technical approaches.

Patients and methods  A retrospective single-center study of all patients who underwent EDGE procedures between February 2018 and November 2019. Primary outcomes included comparing the technical and clinical success, AEs, and lumen-apposing metal stent (LAMS) migration rates per access route (gastrogastric vs jejuno-gastric), number of procedure stages (single-stage vs …

Antimicrobial Susceptibility Testing For Helicobacter Pylori Is Now Widely Available: When, How, Why, David Y Graham, Steven F Moss

Faculty, Staff and Students Publications

No abstract provided.

Atomic Structure Of The Predominant Gii4 Human Norovirus Capsid Reveals Novel Stability And Plasticity, Liya Hu, Wilhelm Salmen, Rong Chen, Yi Zhou, Frederick Neill, James E Crowe, Robert L Atmar, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, and GII.4 virus-like particles (VLPs) are being used in vaccine development. The atomic structure of the GII.4 capsid in the native T = 3 state has not been determined. Here we present the GII.4 VLP structure with T = 3 symmetry determined using X-ray crystallography and cryo-EM at 3.0 Å and 3.8 Å resolution, respectively, which reveals unanticipated novel features. A novel aspect in the crystal structure determined without imposing icosahedral symmetry is the remarkable adaptability of the capsid protein VP1 …

Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A Siddiqui, Jesse L Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

Mucins are components of the mucus layer overlying the intestinal epithelial cells, which maintains physiological homeostasis. Altered mucin expression is associated with disease progression. Expression of MUC4 decreases in colorectal cancer (CRC); however, its functional role and implications in the intestinal pathology in CRC are not studied well. Therefore, we generated a genetically engineered Muc4 knockout (Muc4-/-) CRC mouse model by crossing with Muc4-/- and Apc^flox/flox mice in the presence of colon-specific inducible Cre. We observed that deficiency of Muc4 results in an increased number of macroscopic tumors in the colon and rectal region and leads to poor survival. …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Randomised Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain, Robert J Shulman, Bruno P Chumpitazi, Susan M Abdel-Rahman, Uttam Garg, Salma Musaad, Gregory L Kearns

Faculty, Staff and Students Publications

AIMS: Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.

METHODS: Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, …

Effect Of Domperidone Therapy On Gastroparesis Symptoms: Results Of A Dynamic Cohort Study By Niddk Gastroparesis Consortium, Irene Sarosiek, Mark Van Natta, Henry P Parkman, Thomas Abell, Kenneth L Koch, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Madhusudan Grover, Frank A Hamilton, Pankaj J Pasricha, Katherine P Yates, Laura Miriel, Laura Wilson, Goro Yamada, James Tonascia, Richard W Mccallum

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR).

METHODS: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. …

Constipation In Patients With Symptoms Of Gastroparesis: Analysis Of Symptoms And Gastrointestinal Transit, Henry P Parkman, Emily Sharkey, Richard W Mccallum, William L Hasler, Kenneth L Koch, Irene Sarosiek, Thomas L Abell, Braden Kuo, Robert J Shulman, Madhusudan Grover, Gianrico Farrugia, Ron Schey, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Nih/Niddk Gastroparesis Consortium

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC).

METHODS: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper …

Cross-Roads For Meta-Analysis And Network Meta-Analysis Of H Pylori Therapy, David Y Graham, Ruben Hernaez, Theodore Rokkas

Faculty, Staff and Students Publications

Helicobacter pylori infections are responsible for tremendous morbidity and mortality worldwide, leading to efforts to eradicate the organism. However, the effectiveness of antimicrobial therapy has been undermined by the progressive development of antimicrobial resistance. Treatments and treatment guidelines have been based on traditional pairwise meta-analyses of randomized controlled trials. More recently, network meta-analyses have also been utilized in an attempt to provide useful information to the clinician regarding which therapies appear best and which to avoid as the least efficacious. However, both forms of meta-analysis have been undermined by the same problems including the poor quality of the clinical trials …

Regulation Of The Double-Stranded Rna Response Through Adar1 Licenses Metaplastic Reprogramming In Gastric Epithelium, José B Sáenz, Nancy Vargas, Charles J Cho, Jason C Mills

Faculty, Staff and Students Publications

Cells recognize both foreign and host-derived double-stranded RNA (dsRNA) via a signaling pathway that is usually studied in the context of viral infection. It has become increasingly clear that the sensing and handling of endogenous dsRNA is also critical for cellular differentiation and development. The adenosine RNA deaminase, ADAR1, has been implicated as a central regulator of the dsRNA response, but how regulation of the dsRNA response might mediate cell fate during injury and whether such signaling is cell intrinsic remain unclear. Here, we show that the ADAR1-mediated response to dsRNA was dramatically induced in 2 distinct injury models of …

Rapunzel Syndrome Complicated By Escherichia Coli Sepsis, Bowel Perforation, And Pancreatitis In An 11-Year-Old Malnourished Female, Rhea Daniel, Mary Arbuthnot, Srinivas Ramireddy, Supriya Nair

Faculty, Staff and Student Publications

The most common presenting symptoms of Rapunzel syndrome include abdominal pain (37%), nausea and vomiting (33.3%), obstruction (25.9%), and peritonitis (18.3%). Less commonly, patients may present with weight loss (7.4%) or intussusception (7.4%). Exceedingly rare complications of Rapunzel syndrome include gastric ulceration, obstructive jaundice, and acute pancreatitis as well as other malabsorptive-related complications including protein-losing enteropathy, iron deficiency, and megaloblastic anemia. This report details the case of an 11-year-old female with Rapunzel syndrome complicated by sepsis, a rare complication reported in only 2% of patients.

Multidisciplinary Care For Refractory Pediatric Functional Abdominal Pain Decreases Emergency And Inpatient Utilization, Andrew S Chu, Laura Torres, Grace Kao, Caroyl Gilbert, Evelyn Caro Monico, Bruno P Chumpitazi

Faculty, Staff and Students Publications

Children with refractory functional abdominal pain (FAP) experience functional disability and may utilize emergency department (ED) and/or inpatient services. Whether multidisciplinary programs which help care for children with refractory FAP affect acute healthcare utilization is unknown. A retrospective chart review of children initially evaluated by the outpatient Multidisciplinary Abdominal Pain Program (MAPP) from October 2016 to May 2019 was completed. Patient characteristics and number of ED visits and hospitalizations for abdominal pain in the year prior to versus year after MAPP evaluation were captured. Thirty-eight children (ages 9-17 years [median 13 years]) were included. The median number of ED visits/patient/year …

Race/Ethnicity And Birthplace As Risk Factors For Gastric Intestinal Metaplasia In A Multiethnic United States Population, Mimi C Tan, Taher Jamali, Theresa H Nguyen, Amy Galvan, Robert J Sealock, Anam Khan, Neda Zarrin-Khameh, Ashley Holloman, Ourania Kampagianni, David Henriquez Ticas, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

INTRODUCTION: Several US subgroups have increased risk of gastric cancer and gastric intestinal metaplasia (GIM) and may benefit from targeted screening. We evaluated demographic and clinical risk factors for GIM and examined the interaction between race/ethnicity and birthplace on GIM risk.

METHODS: We identified patients who had undergone esophagogastroduodenoscopy with gastric biopsy from 3/2006-11/2016 using the pathology database at a safety net hospital in Houston, Texas. Cases had GIM on ≥1 gastric biopsy histopathology, whereas controls lacked GIM on any biopsy. We estimated odds ratios and 95% confidence intervals (CI) for associations with GIM risk using logistic regression and developed …

Comparative Performance Of Risk Prediction Models For Hepatitis B-Related Hepatocellular Carcinoma In The United States, Hyun-Seok Kim, Xian Yu, Jennifer Kramer, Aaron P Thrift, Pete Richardson, Yao-Chun Hsu, Avegail Flores, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Guidelines recommend hepatocellular carcinoma (HCC) surveillance in patients with chronic HBV infection. Several HCC risk prediction models are available to guide surveillance decisions, but their comparative performance remains unclear.

METHODS: Using a retrospective cohort of patients with HBV treated with nucleos(t)ide analogues at 130 Veterans Administration facilities between 9/1/2008 and 12/31/2018, we calculated risk scores from 10 HCC risk prediction models (REACH-B, PAGE-B, m-PAGE-B, CU-HCC, HCC-RESCUE, CAMD, APA-B, REAL-B, AASL-HCC, RWS-HCC). We estimated the models' discrimination and calibration. We calculated HCC incidence in risk categories defined by the reported cut-offs for all models.

RESULTS: Of 3,101 patients …

(#Womeninddw) Persistent Speaker Gender Gap At The Premier Digestive Disease Event, Zubair Khan, Rabia Rukhshan, Asmeen Bhatt, Sushovan Guha, Srinivas Ramireddy, Prithvi Patil, Ricardo Badillo, Roy Tomas Davee, Nirav Thosani

Faculty, Staff and Student Publications

BACKGROUND: Over the last few decades, advances have been made regarding gender equality starting from medical students to trainees, to leadership in academics. The female representation in specialty academic conferences not only reflects the existing gender disparities in that specialty but also can influence young female trainees to join that field. Digestive Disease Week (DDW) is the premier digestive disease event. We aimed to calculate the proportion of female representation among speakers and moderators at the DDW meetings held from 2018 to 2020.

METHODS: The data for DDW 2018-2020 were collected via the online web-based planner. The gender of speakers …

Mapk4 Promotes Triple Negative Breast Cancer Growth And Reduces Tumor Sensitivity To Pi3k Blockade, Wei Wang, Dong Han, Qinbo Cai, Tao Shen, Bingning Dong, Michael T Lewis, Runsheng Wang, Yanling Meng, Wolong Zhou, Ping Yi, Chad J Creighton, David D Moore, Feng Yang

Faculty, Staff and Students Publications

About 15-20% of breast cancer (BCa) is triple-negative BCa (TNBC), a devastating disease with limited therapeutic options. Aberrations in the PI3K/PTEN signaling pathway are common in TNBC. However, the therapeutic impact of PI3K inhibitors in TNBC has been limited and the mechanism(s) underlying this lack of efficacy remain elusive. Here, we demonstrate that a large subset of TNBC expresses significant levels of MAPK4, and this expression is critical for driving AKT activation independent of PI3K and promoting TNBC cell and xenograft growth. The ability of MAPK4 to bypass PI3K for AKT activation potentially provides a direct mechanism regulating tumor sensitivity …