Gastroenterology Commons^™

Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg

Dissertations and Theses (Open Access)

Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …

External Validation Of A Model Determining Risk Of Neoplastic Progression Of Barrett's Esophagus In A Cohort Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Gyanprakash A Ketwaroo, Xianglin L Du, Luis Leon Novelo, Rollin George, Daniel G Rosen, Hashem B El-Serag

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Risk of esophageal adenocarcinoma (EAC) in those with Barrett's esophagus (BE) is 11-fold greater than the general population. It remains unclear which BE patients are at highest risk of progression to EAC. We aimed to validate a predictive model risk-stratifying BE patients.

METHODS: We conducted a retrospective cohort study at the Houston Veteran Affairs Medical Center of consecutive patients with a new diagnosis of BE from November 1990 to January 2019. Study follow-up was through February 2020. Patients were excluded if they had no follow-up EGD with esophageal biopsy sampling after the initial BE-diagnosing EGD or evidence …

Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang

Faculty, Staff and Student Publications

OBJECTIVE: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy.

BACKGROUND: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis.

METHODS: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy …

Management Of Right Sided Carcinoid Heart Failure, Ganesh Arun, Ismat Cheema, Lorrie Pennfield, Mohammed Raza, Erik Raborn, Ami Patel, Farhan Ali

Advances in Clinical Medical Research and Healthcare Delivery

Carcinoid heart disease is a rare complication of an already rare disease. This issue is theorized to be secondary to released proinflammatory molecules that deposit on the surfaces of heart valves. These molecules are released from the carcinoid tumor itself and manifest symptoms based on liver, lung and brain function. The detection of 5-HIAA, a breakdown source of serotonin, is useful for diagnosis. These deposits occur most commonly on the endocardium of valvular cusps and cardiac chambers. This case presents a 48 year old woman with echo findings of right heart failure in the setting of a carcinoid tumor. It …

Differential Effects Of Dietary Macronutrients On The Development Of Oncogenic Kras-Mediated Pancreatic Ductal Adenocarcinoma, Liang Zhu, Juntao Ji, Jianjia Ma, Dan Wang, Muyun Liu, James Xianxing Du, Rong Chen, Wei Hou, James L Abbruzzese, Craig D Logsdon, Vincent W Yang, Yongde Luo, Weiqin Lu

Faculty, Staff and Student Publications

KRAS mutations are prevalent in patients with pancreatic ductal adenocarcinoma (PDAC) and are critical to fostering tumor growth in part by aberrantly rewiring glucose, amino acid, and lipid metabolism. Obesity is a modifiable risk factor for pancreatic cancer. Corroborating this epidemiological observation, mice harboring mutant KRAS are highly vulnerable to obesogenic high-fat diet (HFD) challenges leading to the development of PDAC with high penetrance. However, the contributions of other macronutrient diets, such as diets rich in carbohydrates that are regarded as a more direct source to fuel glycolysis for cancer cell survival and proliferation than HFD, to pancreatic tumorigenesis remain …

Resistant Maltodextrin Consumption In A Double-Blind, Randomized, Crossover Clinical Trial Induces Specific Changes In Potentially Beneficial Gut Bacteria, Volker Mai, Alyssa M Burns, Rebecca J Solch, Jennifer C Dennis-Wall, Maria Ukhanova, Bobbi Langkamp-Henken

Faculty, Staff and Student Publications

Background: We have previously reported that the addition of resistant maltodextrin (RMD), a fermentable functional fiber, to the diet increases fecal weight as well as the amount of fecal bifidobacteria. Here, we report on the targeted analysis of changes in potentially beneficial gut bacteria associated with the intervention. Objective: The primary objective of this study was to determine the effect of adding 0, 15 and 25 g RMD to the diets of healthy free-living adults on potentially beneficial gut bacteria. Methods: We expanded on our previously reported microbiota analysis in a double-blind, placebo-controlled feeding study (NCT02733263) by performing additional qPCR …

Identification Of Multiple Hub Genes In Acute Kidney Injury After Kidney Transplantation By Bioinformatics Analysis, Sang Wook Kang, Sung Wook Kang, Ju Yeon Ban, Min Su Park

School of Graduate Studies Faculty Publications

Background and Objectives: The molecular mechanisms of the development of acute kidney injury (AKI) after kidney transplantation are not yet clear. The aim of this study was to confirm the genes and mechanisms related to AKI after transplantation. Materials and Methods: To investigate potential genetic targets for AKI, an analysis of the gene expression omnibus database was used to identify key genes and pathways. After identification of differentially expressed genes, Kyoto En-cyclopedia of Genes and Genome pathway enrichment analyses were performed. We identified the hub genes and established the protein–protein interaction network. Results: Finally, we identified 137 differentially expressed genes …

Rapid Molecular Diagnostics Of Tuberculosis Resistance By Targeted Stool Sequencing, Doctor B Sibandze, Alexander Kay, Viola Dreyer, Welile Sikhondze, Qiniso Dlamini, Andrew Dinardo, Godwin Mtetwa, Bhekumusa Lukhele, Debrah Vambe, Christoph Lange, Muyalo Glenn Dlamini, Tara Ness, Rojelio Mejia, Barbara Kalsdorf, Jan Heyckendorf, Martin Kuhns, Florian P Maurer, Sindisiwe Dlamini, Gugu Maphalala, Stefan Niemann, Anna Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: Stool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.

METHODS: We evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a …

An Observational Retrospective Study Of Adverse Events And Behavioral Outcomes During Pediatric Dental Sedation, Kawtar Zouaidi, Gregory Olson, Helen H Lee, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Purpose: The purpose of this study was to examine a university-based dental electronic health records (EHR) database to identify sedation-related adverse events (AEs) and assess patients' behavioral outcomes during routine pediatric dental sedations (PDSs) in a dental school clinic.

Methods: A database was screened for patients younger than 18 years old who had received dental sedation in 2019. The qualifying EHRs were then accessed and sedations were reviewed for AEs, which were categorized using a 12-point classification system and the Tracking and Reporting Outcomes of Procedural Sedation Tool. Patient behaviors were assessed using provider progress notes and categorized as presence/ …

Lncrnas Uc145 And Prkg1-As1 Determine The Functional Output Of Dkk1 In Regulating The Wnt Signaling Pathway In Gastric Cancer, Jung-Ho Yoon, Hyojoo Byun, Cristina Ivan, George A Calin, Dahyun Jung, Sangkil Lee

Faculty, Staff and Student Publications

DKK1 inhibits the canonical Wnt signaling pathway that is known to be involved in various cancers. However, whether DKK1 acts as an oncogene or tumor suppressor gene remains controversial. Furthermore, the DKK1-regulating mechanism in gastric cancer has not yet been defined. The aim of this study was to explore whether the ultraconserved region UC.145 regulates epigenetic changes in DKK1 expression in gastric cancer. Microarray analysis revealed that UC.145 exhibited the highest binding affinity to EZH2, a histone methyltransferase. The effects of UC.145 inactivation were assessed in gastric cancer cell lines using siRNA. The results indicated that UC.145 triggers DKK1 methylation …

Evaluation Of Heat Inactivation Of Human Norovirus In Freshwater Clams Using Human Intestinal Enteroids, Tsuyoshi Hayashi, Yoko Yamaoka, Atsushi Ito, Takashi Kamaishi, Ryuichi Sugiyama, Mary K Estes, Masamichi Muramatsu, Kosuke Murakami

Faculty, Staff and Students Publications

Foodborne disease attributed to the consumption of shellfish contaminated with human norovirus (HuNoV) is one of many global health concerns. Our study aimed to determine the conditions of the heat-inactivation of HuNoV in freshwater clams (Corbicula japonica) using a recently developed HuNoV cultivation system employing stem-cell derived human intestinal enteroids (HIEs). We first measured the internal temperature of the clam tissue in a water bath during boiling at 90 °C and found that approximately 2 min are required for the tissue to reach 90 °C. Next, GII.4 HuNoV was spiked into the center of the clam tissue, followed …

Improving Advanced Therapeutic Endoscopy Performance At An Academic Children's Hospital, Julia Snodgrass, Thomas M. Attard, Donna Ditsch, John Colgan, Amanda Weston, Jessica Koch, Nadia Ibrahimi, Pang Krasaelap, Voytek Slowick, Laura Shroyer

Research Days

Problem Statement/Question: Advanced therapeutic endoscopy is infrequently needed but critical in the management of children with complex gastroenterology disorders. Hands-on experience in specific advanced techniques, set up of endoscopy equipment and familiarity with new ancillary equipment for use during endoscopy have been intra-departmentally identified as potential areas for improvement.

Background/Project Intent: Our aim is to improve provider scoring on an endoscopy practice test based on technical aspects of therapeutic techniques, indications and set up of standard and new endoscopic equipment by 20% over pre-practice session testing.

Methods: The Model for Improvement framework was utilized. A multidisciplinary team was created including …

Perforating Gastric/Duodenal Ulcer Development Following Roux-En-Y Gastric Bypass Surgery: A Case Series, Sugosh Anur, Michael A. Coscia Iii, Louis Balsama

Rowan-Virtua Research Day

Roux-en-Y gastric bypass is a well-studied procedure resulting in long term weight loss. Due to countless years of study, the morbidity and mortality associated with a Roux en Y gastric bypass has been greatly decreased. However, there are still several rare, yet serious, complications that may arise in the post-operative period. Anastomotic leaks and ulcers are just two of those complications. We describe a case of a 41 year old female developing postoperative perforated duodenal ulcer. A laparoscopic repair was performed using a Graham patch technique. This review aims to identify factors contributing to the ulcer development as well as …

Case Report: Epigastric Abdominal Pain From Beverage Ingestion Of Freshly Squeezed Juice Of The Hardy Orange Flying Dragon Plant (Poncirus Trifoliata), James Espinosa, Alan Lucerna, David Ho

Rowan-Virtua Research Day

We report the case of a 25 year old male who presented to the ED with epigastric abdominal pain after ingesting a freshly squeezed beverage form of Flying Dragon Hardy Orange plant (Poncirus trifoliata). Poison control was contacted and recommended symptomatic treatment only. The patient’s pain resolved while in the emergency department. Seed and rind preparations have been used as an herbal remedy in East Asia. Freshly squeezed Poncirus trifoliata can cause significant abdominal pain.

A Case Report Of Suspected Choledocholithiasis 20 Years After Cholecystectomy, Maleeha Memon, Dhara Rana, Chandni Patel, Christine Leroy, Bijal Sheth

Rowan-Virtua Research Day

Gallstones are a common prevalence in western societies where approximately 15% of Americans have gallstones. The mainstay treatment for symptomatic cholelithiasis is laparoscopic cholecystectomy. It is estimated approximately 650,000 to 700,000 cholecystectomies are performed every year. Most patients feel relief after a laparoscopic cholecystectomy, but a small number of patients experience post cholecystectomy syndrome, which presents as biliary colic pain. Although the pathophysiology of the post cholecystectomy syndrome is unclear, one theory proposes that it is due to the alteration in bile flow after the removal of the gallbladder, which serves as a reservoir for bile. This bile is thought …

Novel Fold Of Rotavirus Glycan-Binding Domain Predicted By Alphafold2 And Determined By X-Ray Crystallography, Liya Hu, Wilhelm Salmen, Banumathi Sankaran, Yi Lasanajak, David F Smith, Sue E Crawford, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a β-sheet clasping …

Angiotensin Receptor Blockers Associated Enteropathy- Brief Report, Falgun Gosai, Neha Gosai

Journal of Community Hospital Internal Medicine Perspectives

The current literature has shown equivocal results regarding the association of Olmesartan and other angiotensin receptor blockers (ARBs) use and the presence of Celiac sprue-like enteropathy (CSLE). Various factors affecting the association are- patient population under study, geographic area, and duration of use of medication. Various case reports/ case series and observational studies have shown the mixed results regarding an association. We have tried to answer a question what exists in the literature regarding the angiotensin receptor blockers related sprue like enteropathy.

Necrotizing Enterocolitis Rates In Preterm Infants, Alexis Howard

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Breast milk and donor human milk is used in the prevention of necrotizing enterocolitis (NEC) in preterm infants born prior to 37 weeks gestation and those with very low birth weight. This process occurs through direct breast feeding and tube feeding. The aim of this study was to compare the use of breast milk and donor milk to the use of formula feed in preterm infants. A systematic review was conducted using articles collected from CINAHL and PubMed and was guided by PRISMA guidelines. A total of 15 studies that met criteria were analyzed by purpose, variables, study design, population …

Intestinal Tuberculosis Presenting With Gastrointestinal Bleeding In Patient On Warfarin Therapy, Pascal Kuka, Joe Rakiro, Joseph Gatheru, Felix Riunga

Internal Medicine, East Africa

Background: Intestinal tuberculosis (ITB) constitutes less than 5% of overall cases of extrapulmonary disease and mostly affects the ileocecal region. The presentation and radiologic findings in enteric tuberculosis can mimic Crohn’s disease (CD).

Case Pre- sentation: We present a case report of an African woman who presented to a Kenyan hospital with lower gastrointestinal bleeding while on anticoagulation for valvular atrial fibrillation, and was diagnosed with intestinal tuberculosis after colonoscopy, biopsy, and positive staining for tuberculous bacilli.

Conclusion: Intestinal tuberculosis causing gastrointestinal bleeding is rare but should be suspected in patients living in TB endemic regions.

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations and Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …