Gastroenterology Commons^™

Implementing Molecular Tuberculosis Diagnostic Methods In Limited-Resource And High-Burden Countries, Anca Vasiliu, Antonia Morita Iswari Saktiawati, Raquel Duarte, Christoph Lange, Daniela Maria Cirillo

Faculty, Staff and Students Publications

Tuberculosis (TB) is one of the deadliest infectious diseases in the world with more than a million people dying of TB each year. Accurate and timely TB diagnosis has the potential to alleviate the global TB burden; therefore, one of the pillars of the End TB Strategy developed by the World Health Organization (WHO) is the early diagnosis of TB, including universal drug-susceptibility testing (DST). The WHO emphasises the importance of DST before treatment initiation, using molecular WHO-recommended rapid diagnostic tests (mWRDs). Currently available mWRDs are nucleic acid amplification tests, line probe assays, whole genome sequencing, and targeted next-generation sequencing. …

Risk Factors And Prognostic Significance Of Anemia In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Amanda Grimes, Gladstone Airewele, Shaun Bulsara, Taylor Olmsted Kim, Heather Haq, Erin Peckham-Gregory, Sebastian R Wanless, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Jenny Despotovic, Michael Scheurer

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH).

DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014.

METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival.

RESULTS: Two thousand, one hundred and thirty-seven children were …

Early Phase Trial Of Intracystic Injection Of Large Surface Area Microparticle Paclitaxel For Treatment Of Mucinous Pancreatic Cysts, Mohamed Othman, Kalpesh Patel, Somashekar G Krishna, Antonio Mendoza-Ladd, Shelagh Verco, Wasif Abidi, James Verco, Alison Wendt, Gere Dizerega

Faculty, Staff and Students Publications

Background and study aims  Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated.

Patients and methods  Ten subjects with confirmed PCLs (size > 1.5 cm) received intracystic LSAM-PTX via EUS-FNI at volumes equal to those aspirated from the cyst in sequential cohorts at 6, 10, and 15 mg/mL in a standard …

Simultaneous Use Of Endobronchial And Endoscopic Ultrasound Guidance As Primary Tools In The Diagnosis Of Malignant Pleural Mesothelioma, Babith Mankidy, Jordan Sparkman, Shreyes Boddu, Quillann Huang, Munish Sharma

Faculty, Staff and Students Publications

Malignant pleural mesothelioma (MPM) is related to exposure to asbestos. It is insidious in nature and is generally diagnosed at an advanced stage. MPM is aggressive and portends a poor prognosis. Definitive diagnosis is usually established by obtaining pathological samples of the pleura by medical or surgical thoracoscopy. However, these procedures are invasive and carry a risk of seeding of biopsy sites with tumors. We herein report an infrequently encountered case of simultaneous use of endobronchial ultrasound and endoscopic ultrasound-guided biopsy of malignant pleural mesothelioma in a 48-year-old female patient.

Comparative Effectiveness Of Surveillance Colonoscopy Intervals On Colorectal Cancer Outcomes In A National Cohort Of Patients With Inflammatory Bowel Disease, Hyun-Seok Kim, Ruben Hernaez, Shubhada Sansgiry, Akbar K Waljee, Frank I Scott, James D Lewis, Hashem B El-Serag, Jason K Hou

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown.

METHODS: We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 >year, …

Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning

Graduate Theses and Dissertations (2019 - present)

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one …

A Phase Ii Randomized Double Blinded Trial Evaluating The Efficacy Of Curcumin With Pre-Operative Chemoradiation For Rectal Cancer, Jillian R Gunther, Awalpreet S Chadha, Sushovan Guha, Gottumukkala S Raju, Dipen M Maru, Mark F Munsell, Yan Jiang, Peiying Yang, Edd Felix, Marilyn Clemons, Geena George Mathew, Pankaj K Singh, John M Skibber, Miguel A Rodriguez-Bigas, George J Chang, Cathy Eng, Marc E Delclos, Christopher H Crane, Prajnan Das, Sunil Krishnan

Faculty, Staff and Student Publications

Background

In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods

From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. …

Evaluation Of Murine Host Sex As A Biological Variable In Transplanted Human Intestinal Organoid Development, Eoin P Mcneill, Vikas S Gupta, David J Sequeira, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Background: Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.

Aims: We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.

Methods: HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8-9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR …

Clinically Significant Metachronous Colorectal Pathology Detected Among Young-Onset Colorectal Cancer Survivors: Implications For Post-Resection Surveillance Guidelines, Oliver Peacock, Eduardo Vilar, Montserrat Guraieb-Trueba, Selvi Thirumurthi, George J Chang, Y Nancy You

Faculty, Staff and Student Publications

No abstract provided.

A Phase Ii Randomized Double Blinded Trial Evaluating The Efficacy Of Curcumin With Pre-Operative Chemoradiation For Rectal Cancer, Jillian R Gunther, Awalpreet S Chadha, Sushovan Guha, Gottumukkala S Raju, Dipen M Maru, Mark F Munsell, Yan Jiang, Peiying Yang, Edd Felix, Marilyn Clemons, Geena George Mathew, Pankaj K Singh, John M Skibber, Miguel A Rodriguez-Bigas, George J Chang, Cathy Eng, Marc E Delclos, Christopher H Crane, Prajnan Das, Sunil Krishnan

Faculty, Staff and Student Publications

Background: In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods: From 2008-2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood …

Consensus Subtypes Of Hepatocellular Carcinoma Associated With Clinical Outcomes And Genomic Phenotypes, Sung Hwan Lee, Sun Young Yim, Yun Seong Jeong, Qi-Xiang Li, Sang-Hee Kang, Bo Hwa Sohn, Shwetha V Kumar, Ji-Hyun Shin, You Rhee Choi, Jae-Jun Shim, Hayeon Kim, Ji Hoon Kim, Shin Kim, Sheng Guo, Randy L Johnson, Ahmed Kaseb, Koo Jeong Kang, Yun Shin Chun, Hee Jin Jang, Byoung Gill Lee, Hyun Goo Woo, Min Jin Ha, Rehan Akbani, Lewis R Roberts, David A Wheeler, Ju-Seog Lee

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Although many studies revealed transcriptomic subtypes of HCC, concordance of the subtypes are not fully examined. We aim to examine a consensus of transcriptomic subtypes and correlate them with clinical outcomes.

APPROACH AND RESULTS: By integrating 16 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes. STM (STeM) is characterized by high stem cell features, vascular invasion, and poor prognosis. CIN (Chromosomal INstability) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity. BCM (Beta-Catenin with high Male …

Neoadjuvant Chemotherapy Is Associated With Altered Immune Cell Infiltration And An Anti-Tumorigenic Microenvironment In Resected Pancreatic Cancer, Andressa Dias Costa, Sara A Väyrynen, Akhil Chawla, Jinming Zhang, Juha P Väyrynen, Mai Chan Lau, Hannah L Williams, Chen Yuan, Vicente Morales-Oyarvide, Dalia Elganainy, Harshabad Singh, James M Cleary, Kimberly Perez, Kimmie Ng, William Freed-Pastor, Joseph D Mancias, Stephanie K Dougan, Jiping Wang, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Lauren Brais, Emma Reilly, Thomas Clancy, David C Linehan, Daniel T Chang, Aram F Hezel, Albert C Koong, Andrew J Aguirre, Brian M Wolpin, Jonathan A Nowak

Faculty, Staff and Student Publications

PURPOSE: Neoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood.

DESIGN: We employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient …

Progress In Gastroparesis - A Narrative Review Of The Work Of The Gastroparesis Clinical Research Consortium, Pankaj J Pasricha, Madhusudan Grover, Katherine P Yates, Thomas L Abell, Kenneth L Koch, Richard W Mccallum, Irene Sarosiek, Cheryl E Bernard, Braden Kuo, Robert Bulat, Robert J Shulman, Bruno P Chumpitazi, James Tonascia, Laura A Miriel, Laura A Wilson, Mark L Van Natta, Emily Mitchell, Frank Hamilton, Gianrico Farrugia, Henry P Parkman, Niddk/Nih Gpcrc Consortium

Faculty, Staff and Students Publications

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders.

Genetic And Small-Molecule Modulation Of Stat3 In A Mouse Model Of Crohn's Disease, Prema Robinson, Emily Magness, Kelsey Montoya, Nikita Engineer, Thomas K Eckols, Emma Rodriguez, David J Tweardy

Faculty, Staff and Student Publications

Crohn's disease (CD), is an inflammatory bowel disease that can affect any part of the gastro-intestinal tract (GI) and is associated with an increased risk of gastro-intestinal cancer. In the current study, we determined the role of genetic and small-molecule modulation of STAT3 in a mouse model of CD. STAT3 has 2 isoforms (α, β) which are expressed in most cells in a 4:1 ratio (α: β). STAT3α has pro-inflammatory and anti-apoptotic functions, while STAT3β has contrasting roles. We used an animal model of CD consisting of intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid and examined the severity of CD in …

Metabolic Targeting Of Nrf2 Potentiates The Efficacy Of The Trap1 Inhibitor G-Tpp Through Reduction Of Ros Detoxification In Colorectal Cancer, Hong-Yuan Tsai, Mary P Bronner, Jordon K March, John F Valentine, Noah F Shroyer, Lisa A Lai, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between …

Tuberculous Salpingitis - Possible Cause Of Salpingo-Enteric Fistula, Shayan Sirat Maheen Anwar, Anam Khan, Fahd Haroon, Frawa Mohsin

Department of Radiology

Salpingo-enteric fistula is a rare disease causing infertility. It occurs when there is a connection between fallopian tube and the intestine. It can be accurately diagnosed with hysterosalpingography. Fistulas mostly occur as a consequence of obstetric complications, however, inflammatory bowel disease, pelvic malignancy, pelvic radiation therapy, iatrogenic causes, and trauma are other potential causes. The possibility of tuberculous salpingitis as a possible cause of salpingo-enteric fistula should always be considered in the developing countries where tuberculosis is endemic.

Coating Formulation Change Leads To Inferior Performance Of Long-Lasting Insecticidal Nets In Papua New Guinea, Nakei Bubun, Evodia Anetul, Melanie Koinari, Timothy W Freeman, Stephan Karl

Faculty, Staff and Student Publications

BACKGROUND: Long-lasting insecticidal nets (LLINs) play a key role in reducing malaria transmission in endemic countries. In a previous study, the authors demonstrated a substantial decrease in the bioefficacy of LLINs for malaria prevention delivered to Papua New Guinea (PNG) between 2013 and 2019. This coincided with a rise in malaria cases in the country. The present study was aimed at determining the underlying cause of the reduced bioefficacy observed in these LLINs. The main hypothesis was that a change in the coating formulation of the respective LLIN product was responsible, and had led to significantly altered product properties and …

Acafinder: Genome Mining For Anti-Crispr-Associated Genes, Bowen Yang, Jinfang Zheng, Yanbin Yin

Food for Health: Publications

Anti-CRISPR (Acr) proteins are encoded by (pro)viruses to inhibit their host’s CRISPR-Cas systems. Genes encoding Acr and Aca (Acr associated) proteins often colocalize to form acr-aca operons. Here, we present AcaFinder as the first Aca genome mining tool. AcaFinder can (i) predict Acas and their associated acr-aca operons using guilt-by-association (GBA); (ii) identify homologs of known Acas using an HMM (Hidden Markov model) database; (iii) take input genomes for potential prophages, CRISPR-Cas systems, and self-targeting spacers (STSs); and (iv) provide a standalone program (https://github.com/boweny920/AcaFinder) and a web server (http://aca .unl.edu/Aca). AcaFinder was applied to mining over …

Effect Of Selective Decontamination Of The Digestive Tract On Hospital Mortality In Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial, The Suddicu Investigators For The Australian And New Zealand Intensive Care Society Clinical Trials Group, John A Myburgh, Ian M Seppelt, Fiona Goodman, Laurent Billot, Maryam Correa, Joshua S Davis, Anthony C Gordon, Naomi E Hammond, Jon Iredell, Qiang Li, Sharon Micallef, Jennene Miller, Jayanthi Mysore, Colman Taylor, Paul J Young, Brian H Cuthbertson, Simon R Finfer

Faculty, Staff and Student Publications

IMPORTANCE: Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain.

OBJECTIVE: To determine whether SDD reduces in-hospital mortality in critically ill adults.

DESIGN, SETTING, AND PARTICIPANTS: A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021.

INTERVENTIONS: ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a …

Oral N-Acetyl Cysteine Versus Rectal Indomethacin For Prevention Of Post Ercp Pancreatitis: A Multicenter Multinational Randomized Controlled Trial, Pezhman Alavinejad, Nguyen-Phuong Nhu Tran, Omid Eslami, Omar El Shaarawy, Omar El Shaarawy, Ahmad Hormati, Seied Saeed Seiedian, Abazar Parsi, Mohammed Hussien Ahmed, Amna Subhan Butt

Section of Gastroenterology

Background: This multicenter multinational RCT designed to compare the efficacy of suppository indomethacin and NAC for prevention of PEP.
Methods: During a 6-month period, all of the ERCP cases in seven referral centers were randomly assigned to receive either 1200 mg oral NAC, indomethacin suppository 100 mg, 1200 mg oral NAC plus indomethacin suppository 100 mg or placebo 2 hours before ERCP. The primary outcomes were the rate and severity of any PEP.
Results: A total of 432 patients included (41.4% male). They were originally citizens of 6 countries (60.87% Caucasian). They were randomly allocated to receive either NAC (group …