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Full-Text Articles in Digestive System Diseases

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang Aug 2022

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang

Faculty, Staff and Student Publications

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a …


A Differential Diagnosis Of Unusual Gastric Ulcer, Soo-Yoon Sung, Hyun Ho Choi, Kyung Jin Seo Aug 2022

A Differential Diagnosis Of Unusual Gastric Ulcer, Soo-Yoon Sung, Hyun Ho Choi, Kyung Jin Seo

Faculty, Staff and Student Publications

The endoscopic findings of diffuse large B cell lymphoma have various presentations. In our case, the patient had developed multiple elevated central ulceration lesions, and the peripheral elevated portion had a heaped-up margin. The margin had a sharp, smooth edge that was not infiltrative and could be confused with a simple gastric ulcer. Endoscopists should be aware of the possibility of multiple lymphoma ulcers with heaped-up margins. We present some unusual endoscopic features of lymphoma, which are easily misdiagnosed as gastric ulcers.


Spectral Library-Based Single-Cell Proteomics Resolves Cellular Heterogeneity, Lakmini Senavirathna, Cheng Ma, Ru Chen, Sheng Pan Aug 2022

Spectral Library-Based Single-Cell Proteomics Resolves Cellular Heterogeneity, Lakmini Senavirathna, Cheng Ma, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

Dissecting the proteome of cell types and states at single-cell resolution, while being highly challenging, has significant implications in basic science and biomedicine. Mass spectrometry (MS)-based single-cell proteomics represents an emerging technology for system-wide, unbiased profiling of proteins in single cells. However, significant challenges remain in analyzing an extremely small amount of proteins collected from a single cell, as a proteome-wide amplification of proteins is not currently feasible. Here, we report an integrated spectral library-based single-cell proteomics (SLB-SCP) platform that is ultrasensitive and well suited for a large-scale analysis. To overcome the low MS/MS signal intensity intrinsically associated with a …


The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia Aug 2022

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …


Identifying Factors Associated With Detection Of Sessile Gastric Polyps In Patients With Familial Adenomatous Polyposis, Gautam N Mankaney, Michael Cruise, Shashank Sarvepalli, Amit Bhatt, David Liska, Carol A Burke Aug 2022

Identifying Factors Associated With Detection Of Sessile Gastric Polyps In Patients With Familial Adenomatous Polyposis, Gautam N Mankaney, Michael Cruise, Shashank Sarvepalli, Amit Bhatt, David Liska, Carol A Burke

Faculty, Staff and Students Publications

Background and study aims  Gastric cancer (GC) is increasingly reported and a leading cause of death in patients with familial adenomatous polyposis (FAP). Identifying features in patients with FAP who harbor sessile gastric polyps, likely precursors to GC, may lead to alterations in endoscopic surveillance in those patients and allow endoscopic intervention to decrease the risk of GC. The aim of this study was to identify demographic and clinical factors in patients with FAP who harbor sessile gastric polyps.

Patients and methods  We retrospectively compared demographic, clinical, and endoscopic features in consecutive adult patients with FAP who presented for a …


Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network Aug 2022

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …


A Novel Approach To The Removal Of A Silastic Band Via The Peroral Endoscopic Tunneling-Silastic Bandectomy Technique, Wasif M Abidi, Salmaan Jawaid Aug 2022

A Novel Approach To The Removal Of A Silastic Band Via The Peroral Endoscopic Tunneling-Silastic Bandectomy Technique, Wasif M Abidi, Salmaan Jawaid

Faculty, Staff and Students Publications

The peroral endoscopic tunneling-silastic bandectomy technique to remove a silastic band causing a vertical banded gastroplasty stenosis. This method is a viable alternative to surgical removal of foreign bodies outside the gastrointestinal lumen.


Proteomes Of Extracellular Vesicles From Pancreatic Cancer Cells And Cancer-Associated Fibroblasts, Sharon Pan, Lisa A Lai, Diane M Simeone, David W Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A Brentnall Aug 2022

Proteomes Of Extracellular Vesicles From Pancreatic Cancer Cells And Cancer-Associated Fibroblasts, Sharon Pan, Lisa A Lai, Diane M Simeone, David W Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A Brentnall

Faculty, Staff and Students Publications

OBJECTIVES: Extracellular vesicles (EVs) are lipid bound vesicles secreted by cells into the extracellular environment. Studies have implicated EVs in cell proliferation, epithelial-mesenchymal transition, metastasis, angiogenesis, and mediating the interaction of tumor cells and microenvironment. A systematic characterization of EVs from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) would be valuable for studying the roles of EV proteins in pancreatic tumorigenesis.

METHODS: Proteomic and functional analyses were applied to characterize the proteomes of EVs released from 5 pancreatic cancer lines, 2 CAF cell lines, and a normal pancreatic epithelial cell line (HPDE).

RESULTS: More than 1400 nonredundant proteins were identified …


Pathological Implication Of Protein Post-Translational Modifications In Cancer, Sheng Pan, Ru Chen Aug 2022

Pathological Implication Of Protein Post-Translational Modifications In Cancer, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Protein post-translational modifications (PTMs) profoundly influence protein functions and play crucial roles in essentially all cell biological processes. The diverse realm of PTMs and their crosstalk is linked to many critical signaling events involved in neoplastic transformation, carcinogenesis and metastasis. The pathological roles of various PTMs are implicated in all aspects of cancer hallmark functions, cancer metabolism and regulation of tumor microenvironment. Study of PTMs has become an important area in cancer research to understand cancer biology and discover novel biomarkers and therapeutic targets. With a limited scope, this review attempts to discuss some PTMs of high frequency with recognized …


Cell Plasticity In Regeneration In The Stomach And Beyond, Mahliyah Adkins-Threats, Jason C Mills Aug 2022

Cell Plasticity In Regeneration In The Stomach And Beyond, Mahliyah Adkins-Threats, Jason C Mills

Faculty, Staff and Students Publications

Recent studies using cell lineage-tracing techniques, organoids, and single-cell RNA sequencing analyses have revealed: 1) adult organs use cell plasticity programs to recruit progenitor cells to regenerate tissues after injury, and 2) plasticity is far more common than previously thought, even in homeostasis. Here, we focus on the complex interplay of normal stem cell differentiation and plasticity in homeostasis and after injury, using the gastric epithelium as a touchstone. We also examine common features of regenerative programs and discuss the evolutionarily conserved, stepwise process of paligenosis which reprograms mature cells into progenitors that can repair damaged tissue. Finally, we discuss …


An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan Jul 2022

An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer …


Clinical Factors Associated With Non-Obese Nonalcoholic Fatty Liver Disease Detected Among Us Adults In The Nhanes 2017-2018, Zayd Adnan Razouki, Xiaotao Zhang, Jessica P Hwang, Natalia I Heredia Jul 2022

Clinical Factors Associated With Non-Obese Nonalcoholic Fatty Liver Disease Detected Among Us Adults In The Nhanes 2017-2018, Zayd Adnan Razouki, Xiaotao Zhang, Jessica P Hwang, Natalia I Heredia

Faculty, Staff and Student Publications

NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US adults. We aggregated data from the 2017−2018 cycle of NHANES and included adults (age ≥ 20 years) with BMI < 25 kg/m2 with complete data for the survey, medical examination, and VCTE along with controlled attenuation parameter (CAP). We excluded participants with risks of other liver diseases. We considered patients to have non-obese NAFLD if CAP was >285 dB/m, or non-obese NAFLD fibrosis if this CAP criteria was met and liver stiffness was >8.6 kPa. We calculated the adjusted OR and 95% CI for associations with non-obese NAFLD using multivariable logistic regression. The prevalence of non-obese NAFLD was 6.2% and Asian Americans (12.2%) had the highest non-obese NAFLD prevalence. Clinical factors associated with non-obese NAFLD were advanced age and metabolic syndrome (ORadjusted = 6.8, 95% CI 3.0−15.5). In a separate model, we found elevated glucose (ORadjusted = 4.1, 95% CI 2.1−7.9), triglycerides (ORadjusted = 3.8, 95% CI 1.7−8.5), and …


A Phospholipid Mimetic Targeting Lrh-1 Ameliorates Colitis, Suzanne G Mays, Emma H D'Agostino, Autumn R Flynn, Xiangsheng Huang, Guohui Wang, Xu Liu, Elizabeth J Millings, C Denise Okafor, Anamika Patel, Michael L Cato, Jeffery L Cornelison, Diana Melchers, René Houtman, David D Moore, John W Calvert, Nathan T Jui, Eric A Ortlund Jul 2022

A Phospholipid Mimetic Targeting Lrh-1 Ameliorates Colitis, Suzanne G Mays, Emma H D'Agostino, Autumn R Flynn, Xiangsheng Huang, Guohui Wang, Xu Liu, Elizabeth J Millings, C Denise Okafor, Anamika Patel, Michael L Cato, Jeffery L Cornelison, Diana Melchers, René Houtman, David D Moore, John W Calvert, Nathan T Jui, Eric A Ortlund

Faculty, Staff and Students Publications

Phospholipids are ligands for nuclear hormone receptors (NRs) that regulate transcriptional programs relevant to normal physiology and disease. Here, we demonstrate that mimicking phospholipid-NR interactions is a robust strategy to improve agonists of liver receptor homolog-1 (LRH-1), a therapeutic target for colitis. Conventional LRH-1 modulators only partially occupy the binding pocket, leaving vacant a region important for phospholipid binding and allostery. Therefore, we constructed a set of molecules with elements of natural phospholipids appended to a synthetic LRH-1 agonist. We show that the phospholipid-mimicking groups interact with the targeted residues in crystal structures and improve binding affinity, LRH-1 transcriptional activity, …


Unexpected Movement Of The Esophagus Across The Aorta, Hyun Ho Choi, Soo-Yoon Sung, Yoon Ho Ko Jul 2022

Unexpected Movement Of The Esophagus Across The Aorta, Hyun Ho Choi, Soo-Yoon Sung, Yoon Ho Ko

Faculty, Staff and Student Publications

Tumor regression throughout treatment would induce organ movement, but little is known of this in the esophagus. To achieve successful tumor regression, radiation therapy requires several weeks of radiation to be delivered accurately to the tumor. Usually, a 5-10 mm margin is allowed for set-up error and internal organ motion. Our case exhibited an unexpectedly large movement of the esophagus across the aorta with tumor regression that extended outside the margin and thus outside the radiotherapy field. These movements may affect subsequent invasive procedures or treatment during cancer therapy. After the unexpected large movement of the esophagus due to tumor …


Changing Global Epidemiology Of Liver Cancer From 2010 To 2019: Nash Is The Fastest Growing Cause Of Liver Cancer, Daniel Q Huang, Amit G Singal, Yuko Kono, Darren J H Tan, Hashem B El-Serag, Rohit Loomba Jul 2022

Changing Global Epidemiology Of Liver Cancer From 2010 To 2019: Nash Is The Fastest Growing Cause Of Liver Cancer, Daniel Q Huang, Amit G Singal, Yuko Kono, Darren J H Tan, Hashem B El-Serag, Rohit Loomba

Faculty, Staff and Students Publications

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in …


Complex And Simple Appendicitis: Restrictive Or Liberal Postoperative Antibiotic Exposure (Casa Relax) Using Desirability Of Outcome Ranking (Door) And Response Adjusted For Duration Of Antibiotic Risk (Radar): Study Protocol For A Randomized Controlled Trial, Daniel Dante Yeh, Gabrielle E Hatton, Claudia Pedroza, Gerd Pust, Alejandro Mantero, Nicholas Namias, Lillian S Kao Jul 2022

Complex And Simple Appendicitis: Restrictive Or Liberal Postoperative Antibiotic Exposure (Casa Relax) Using Desirability Of Outcome Ranking (Door) And Response Adjusted For Duration Of Antibiotic Risk (Radar): Study Protocol For A Randomized Controlled Trial, Daniel Dante Yeh, Gabrielle E Hatton, Claudia Pedroza, Gerd Pust, Alejandro Mantero, Nicholas Namias, Lillian S Kao

Faculty, Staff and Student Publications

OBJECTIVES: After appendectomy for simple or complicated appendicitis, the optimal duration of postoperative antibiotics (postop abx) is unclear and great practice variability exists. We propose to compare restrictive versus liberal postop abx using a hierarchical composite endpoint which includes patient-centered outcomes and accounts for duration of antibiotic exposure.

METHODS/DESIGN: Participants with simple or complicated appendicitis undergoing appendectomy are randomly assigned to either restricted or liberal strategy. Eligible subjects declining randomization will be recruited to enroll in an observation only cohort. The primary endpoint is an ordinal scale of mutually exclusive clinical outcomes with within-category rankings determined by duration of antibiotic …


Postprandial Symptoms In Patients With Symptoms Of Gastroparesis: Roles Of Gastric Emptying And Accommodation, Henry P Parkman, Mark L Van Natta, Alan H Maurer, Kenneth L Koch, Madhusudan Grover, Zubair Malik, Irene Sarosiek, Thomas L Abell, Robert Bulat, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Richard W Mccallum Jul 2022

Postprandial Symptoms In Patients With Symptoms Of Gastroparesis: Roles Of Gastric Emptying And Accommodation, Henry P Parkman, Mark L Van Natta, Alan H Maurer, Kenneth L Koch, Madhusudan Grover, Zubair Malik, Irene Sarosiek, Thomas L Abell, Robert Bulat, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Richard W Mccallum

Faculty, Staff and Students Publications

Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, …


Mediating Effects Of Neighborhood-Level Socioeconomic Deprivation On The Association Between Race/Ethnicity And Advanced Hepatocellular Carcinoma, Abiodun O Oluyomi, Kusha A Mohammadi, Hashem B El-Serag, Aaron P Thrift Jul 2022

Mediating Effects Of Neighborhood-Level Socioeconomic Deprivation On The Association Between Race/Ethnicity And Advanced Hepatocellular Carcinoma, Abiodun O Oluyomi, Kusha A Mohammadi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Racial/ethnic minorities are more likely than non-Hispanic whites (NHW) to be diagnosed with advanced stage hepatocellular carcinoma (HCC). We examined the role of neighborhood disadvantage as a mediator of the association between race/ethnicity and HCC stage at diagnosis.

METHODS: We used data from HCC cases diagnosed in Texas from 2007 to 2015. HCC cases were classified as local versus regional/advanced stage. A mediation model approach was used to estimate the average direct effect, average mediated (indirect) effect, total effect, and proportion mediated by the Area Deprivation Index (ADI), a composite measure of disadvantage.

RESULTS: 7,622 had local while 6303 …


Cholestasis Alters Brain Lipid And Bile Acid Composition And Compromises Motor Function In Neonatal Piglets, Nicole Lind Henriksen, Svend Høime Hansen, Matthew Domenic Lycas, Xiaoyu Pan, Thomas Eriksen, Lars Søndergaard Johansen, Richard R Sprenger, Christer Stenby Ejsing, Douglas G Burrin, Kerstin Skovgaard, Vibeke Brix Christensen, Thomas Thymann, Stanislava Pankratova Jul 2022

Cholestasis Alters Brain Lipid And Bile Acid Composition And Compromises Motor Function In Neonatal Piglets, Nicole Lind Henriksen, Svend Høime Hansen, Matthew Domenic Lycas, Xiaoyu Pan, Thomas Eriksen, Lars Søndergaard Johansen, Richard R Sprenger, Christer Stenby Ejsing, Douglas G Burrin, Kerstin Skovgaard, Vibeke Brix Christensen, Thomas Thymann, Stanislava Pankratova

Faculty, Staff and Students Publications

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more …


Pilot Phase Results Of A Prospective, Randomized Controlled Trial Of Narrowband Ultraviolet B Phototherapy In Hospitalized Covid-19 Patients, Frank H Lau, Catherine E Powell, Giacomo Adonecchi, Denise M Danos, Andrew R Dinardo, Robert J Chugden, Peter Wolf, Carmen F Castilla Jul 2022

Pilot Phase Results Of A Prospective, Randomized Controlled Trial Of Narrowband Ultraviolet B Phototherapy In Hospitalized Covid-19 Patients, Frank H Lau, Catherine E Powell, Giacomo Adonecchi, Denise M Danos, Andrew R Dinardo, Robert J Chugden, Peter Wolf, Carmen F Castilla

Faculty, Staff and Students Publications

COVID-19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB-UVB) phototherapy is standard of care in a number of immune-dysregulated diseases. To assess the efficacy of NB-UVB phototherapy for improving COVID-19 outcomes in high-risk, hospitalized, we developed the Adaptive Photo-Protection Trial. This is a multi-center, prospective, double-blinded, randomized, placebo-controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB-UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up …


Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu Jul 2022

Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

METHODS: In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. …


United States Healthcare Burden Of Pediatric Functional Gastrointestinal Pain Disorder Hospitalizations From 2002 To 2018, John M Hollier, Jason L Salemi, Robert J Shulman Jul 2022

United States Healthcare Burden Of Pediatric Functional Gastrointestinal Pain Disorder Hospitalizations From 2002 To 2018, John M Hollier, Jason L Salemi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: The healthcare burden of pediatric functional gastrointestinal pain disorders (FGIDs) is unclear. Our study aimed to characterize the burden of these hospitalizations in the United States (US).

METHODS: We utilized the US National Inpatient Sample from 2002 to 2018 to capture pediatric hospitalizations (ages 4 to 18 years old) with a primary discharge diagnosis of abdominal pain, constipation, irritable bowel syndrome, dyspepsia, abdominal migraine, cyclic vomiting syndrome, or fecal incontinence. We calculated the FGID hospitalization prevalence rate, length of stay (LOS), and inflation-adjusted costs annually and assessed for statistically significant trend changes using joinpoint analyses.

KEY RESULTS: 22.3 million …


Pathogenesis Of Tuberculosis: The 1930 Lübeck Disaster Revisited, Peter Donald, Stefan Kaufmann, Stephanie Thee, Anna Maria Mandalakas, Christoph Lange Jun 2022

Pathogenesis Of Tuberculosis: The 1930 Lübeck Disaster Revisited, Peter Donald, Stefan Kaufmann, Stephanie Thee, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

During the 1930 Lübeck Mycobacterium bovis bacille Calmette–Guérin (BCG) disaster, 251 neonates received three oral BCG doses accidentally contaminated by virulent Mycobacterium tuberculosis; 67 (26.7%) infants died of tuberculosis. BCG reversion to pathogenicity did not occur. Detailed post mortem examinations clarified contested aspects of tuberculosis pathogenesis. Gastrointestinal infection was seldom “silent” and did not cause typical primary pulmonary lesions. In 15 infants, primary pulmonary foci were found but these resulted from vaccine ingestion and aspiration and were not caused by gastrointestinal infection spreading to the lungs without trace of its journey, as claimed by prominent researchers such as Calmette …


Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group Jun 2022

Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group

Faculty, Staff and Students Publications

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD.

METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data …


Maternal And Fetal Bile Acid Homeostasis Regulated By Sulfated Progesterone Metabolites Through Fxr Signaling Pathway In A Pregnant Sow Model, Peng Wang, Peiqiang Yuan, Sen Lin, Heju Zhong, Xiaoling Zhang, Yong Zhuo, Jian Li, Lianqiang Che, Bin Feng, Yan Lin, Shengyu Xu, De Wu, Douglas G Burrin, Zhengfeng Fang Jun 2022

Maternal And Fetal Bile Acid Homeostasis Regulated By Sulfated Progesterone Metabolites Through Fxr Signaling Pathway In A Pregnant Sow Model, Peng Wang, Peiqiang Yuan, Sen Lin, Heju Zhong, Xiaoling Zhang, Yong Zhuo, Jian Li, Lianqiang Che, Bin Feng, Yan Lin, Shengyu Xu, De Wu, Douglas G Burrin, Zhengfeng Fang

Faculty, Staff and Students Publications

Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student’s t-test or one-way ANOVA of GraphPad Prism and further compared by using the Student–Newman–Keuls test. Correlation analysis was …


Host Gut Resistome In Gulf War Chronic Multisymptom Illness Correlates With Persistent Inflammation, Dipro Bose, Somdatta Chatterjee, Ethan Older, Ratanesh Seth, Patricia Janulewicz, Punnag Saha, Ayan Mondal, Jeffrey M Carlson, Alan W Decho, Kimberly Sullivan, Nancy Klimas, Stephen Lasley, Jie Li, Saurabh Chatterjee Jun 2022

Host Gut Resistome In Gulf War Chronic Multisymptom Illness Correlates With Persistent Inflammation, Dipro Bose, Somdatta Chatterjee, Ethan Older, Ratanesh Seth, Patricia Janulewicz, Punnag Saha, Ayan Mondal, Jeffrey M Carlson, Alan W Decho, Kimberly Sullivan, Nancy Klimas, Stephen Lasley, Jie Li, Saurabh Chatterjee

Faculty, Staff and Student Publications

Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal …


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 Jun 2022

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 Jun 2022

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 …


Risk For Post-Colonoscopy Irritable Bowel Syndrome In Patients With And Without Antibiotic Exposure: A Retrospective Cohort Study, Ravy K Vajravelu, Jordan M Shapiro, Josephine Ni, Shivani U Thanawala, James D Lewis, Hashem B El-Serag Jun 2022

Risk For Post-Colonoscopy Irritable Bowel Syndrome In Patients With And Without Antibiotic Exposure: A Retrospective Cohort Study, Ravy K Vajravelu, Jordan M Shapiro, Josephine Ni, Shivani U Thanawala, James D Lewis, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Laboratory studies have demonstrated that antibiotic use in conjunction with bowel purgatives causes alterations to the gut microbiota. Because gut microbiota changes may be a trigger for the development of irritable bowel syndrome (IBS), we sought to assess whether individuals who undergo bowel cleansing for colonoscopy and have concurrent antibiotic exposure develop IBS at higher rates than individuals who undergo colonoscopy without antibiotic exposure.

METHODS: We used data from Optum's de-identified Clinformatics Data Mart Database in the United States to study a cohort of 50- to 55-year-olds who underwent screening colonoscopy. Individuals exposed to antibiotics within 14 …


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 Jun 2022

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 Students 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 …