Digestive System Diseases Commons^™

Frailty In End-Stage Liver Disease: Understanding Pathophysiology, Tools For Assessment, And Strategies For Management, Mazen Elsheikh, Ahmed El Sabagh, Islam B Mohamed, Megha Bhongade, Manal M Hassan, Prasun Kumar Jalal

Faculty, Staff and Students Publications

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical …

Decreased Fxr Agonism In The Bile Acid Pool Is Associated With Impaired Fxr Signaling In A Pig Model Of Pediatric Nafld, Magdalena A Maj, Douglas G Burrin, Rodrigo Manjarín

Faculty, Staff and Students Publications

The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with …

Oncogenic Kras Drives Lipofibrogenesis To Promote Angiogenesis And Colon Cancer Progression, Wen-Hao Hsu, Kyle A Labella, Yiyun Lin, Ping Xu, Rumi Lee, Cheng-En Hsieh, Lei Yang, Ashley Zhou, Jonathan M Blecher, Chang-Jiun Wu, Kangyu Lin, Xiaoying Shang, Shan Jiang, Denise J Spring, Yan Xia, Peiwen Chen, John Paul Shen, Scott Kopetz, Ronald A Depinho

Faculty, Staff and Student Publications

Oncogenic KRAS (KRAS*) contributes to many cancer hallmarks. In colorectal cancer, KRAS* suppresses antitumor immunity to promote tumor invasion and metastasis. Here, we uncovered that KRAS* transforms the phenotype of carcinoma-associated fibroblasts (CAF) into lipid-laden CAFs, promoting angiogenesis and tumor progression. Mechanistically, KRAS* activates the transcription factor CP2 (TFCP2) that upregulates the expression of the proadipogenic factors BMP4 and WNT5B, triggering the transformation of CAFs into lipid-rich CAFs. These lipid-rich CAFs, in turn, produce VEGFA to spur angiogenesis. In KRAS*-driven colorectal cancer mouse models, genetic or pharmacologic neutralization of TFCP2 reduced lipid-rich CAFs, lessened tumor angiogenesis, and improved overall survival. …

Spatiotemporal Genomic Profiling Of Intestinal Metaplasia Reveals Clonal Dynamics Of Gastric Cancer Progression, Kie Kyon Huang, Haoran Ma, Roxanne Hui Heng Chong, Tomoyuki Uchihara, Benedict Shi Xiang Lian, Feng Zhu, Taotao Sheng, Supriya Srivastava, Su Ting Tay, Raghav Sundar, Angie Lay Keng Tan, Xuewen Ong, Minghui Lee, Shamaine Wei Ting Ho, Tom Lesluyes, Hassan Ashktorab, Duane Smoot, Peter Van Loo, Joy Shijia Chua, Kalpana Ramnarayanan, Louis Ho Shing Lau, Takuji Gotoda, Hyun Soo Kim, Tiing Leong Ang, Christopher Khor, Jonathan Wei Jie Lee, Stephen Kin Kwok Tsao, Wei Lyn Yang, Ming Teh, Hyunsoo Chung, Jimmy Bok Yan So, Khay Guan Yeoh, Patrick Tan, Singapore Gastric Cancer Consortium

Faculty, Staff and Student Publications

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy …

The Effects Of Night Shift Work On Heart, Gut, And Reproductive Health, A Systematic Review, Courtney Grayson, Preeti Oza

Pacific Journal of Health

Night shift work, a commonplace in today’s society, creates a variety of health-related challenges for individuals who participate in it. Often, the only adverse health effects discussed in relation to night shift work are sleep dysfunction and mental health issues. This systematic review examined the cardiovascular, gastrointestinal, and fertility health effects that plague individuals working night shift. The goal of this work is to illuminate these lesser known, but equally important, health effects in an effort to bring awareness to the issues. By educating night shift workers and health care providers of the acute risks associated with this type of …

Effectiveness Of Conservative Management Versus Laparoscopic Cholecystectomy In The Prevention Of Recurrent Symptoms And Complications In Adults With Uncomplicated Symptomatic Gallstone Disease (C-Gall Trial): Pragmatic, Multicentre Randomised Controlled Trial, Irfan Ahmed, Jemma Hudson, Karen Innes, Rodolfo Hernández, Katie Gillies, Rebecca Bruce, Victoria Bell, Alison Avenell, Jane Blazeby, Miriam Brazzelli, Seonaidh Cotton, Bernard Croal, Mark Forrest, Graeme Maclennan, Peter Murchie, Samantha Wileman, Craig Ramsay, C-Gall Study Group

Faculty, Staff and Student Publications

OBJECTIVE: To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease.

DESIGN: Parallel group, pragmatic randomised, superiority trial.

SETTING: 20 secondary care centres in the UK.

PARTICIPANTS: 434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy.

INTERVENTIONS: Conservative management or surgical removal of the gallbladder.

MAIN OUTCOME MEASURES: The primary patient outcome was quality of life, measured …

Pseudocystic Myxoid Liposarcoma Of The Posterior Chest Wall - A Rare Case Report, Saad Shakil, Sareema Eman Akhtar, Mahum Zaidi, Rizwan Ajmal, Abdulla K. Alsubai, Rahul Ramtohul, Absam Akbar, Aysa Tabassi, Aylin Tabassi, Talal Almas

Medical College Documents

Introduction and importance: Liposarcoma (LPS) is a common soft-tissue sarcoma predominantly diagnosed in adults, arising from malignant adipose cells. Among its various subtypes, myxoid LPS (MLPS) stands out as the second most frequent, accounting for ~30% of all LPS cases. This particular subtype typically manifests in males between the ages of 40 and 50 and is commonly found in the lower extremities. Although rare, MLPS may also occur in the head, neck, and infrequently in the back. Chest wall LPS cases are also sparsely reported.
Case presentation: In this report, we present a case of MLPS in a 69-year-old male …

Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls, Mary Andreae, Mary C. Andreae Mrs

Electronic Theses and Dissertations

Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in …

Nutrition Assessment And Mash Severity In Children Using The Healthy Eating Index, Ajay Kumar Jain, Paula Buchannan, Katherine P Yates, Patricia Belt, Jeffrey B Schwimmer, Philip Rosenthal, Karen F Murray, Jean P Molleston, Ann Scheimann, Stavra A Xanthakos, Cynthia A Behling, Paula Hertel, Jamie Nilson, Brent A Neuschwander-Tetri, James Tonascia, Miriam B Vos, Nonalcoholic Steatohepatitis Clinical Research Network (Nash Crn)

Faculty, Staff and Students Publications

BACKGROUND: Pediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD.

METHODS: Diet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components.

RESULTS: In all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index …

Incidence And Outcomes Of Acute Kidney Injury Including Hepatorenal Syndrome In Hospitalized Patients With Cirrhosis In The Us, Kavish R Patidar, Justin M Belcher, Kevin R Regner, Shelsea A St Hillien, Douglas A Simonetto, Sumeet K Asrani, Javier A Neyra, Pratima Sharma, Juan Carlos Q Velez, Hani Wadei, Mitra K Nadim, Raymond T Chung, Ritu Seethapathy, Xavier Vela Parada, Tianqi Ouyang, Nneka N Ufere, Jevon E Robinson, Paige Mclean Diaz, Robert M Wilechansky, Eric M Przybyszewski, Thomas N Smith, Arzina Aziz Ali, Eric S Orman, Philipp Schulz, Salaah M Siddiqui, Rehma Shabbir, Lucas J Liu, Augusto Cama-Olivares, Alexander H Flannery, Megan L Baker, Deepthi Gunasekaran, Adeline Aswine, Rafik Issa, Jay Li, Shreya Verma, Dustin Chalmers, Vipin Varghese, Walter Lam, Muner Mohamed, Rosemary Kovacic, Anna Gaddy, Rose Mary Attieh, Pedro Cortes, Sahar Semnani, Lin Wang, Saro Khemichian, Andrew S Allegretti

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis.

METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other).

RESULTS: A total of 2,063 patients were included (median age 62 …

Incidence, Clinical Characteristics, And Risk Factors Associated With Recurrent Alcohol-Associated Hepatitis, Kavish R Patidar, Maria Guarnizo Ortiz, James E Slaven, Lauren D Nephew, Eduardo Vilar Gomez, Carla D Kettler, Marwan S Ghabril, Archita P Desai, Eric S Orman, Naga Chalasani, Samer Gawrieh

Faculty, Staff and Students Publications

BACKGROUND: Alcohol relapse occurs frequently in alcohol-associated hepatitis (AH) survivors, but data on the frequency and course of recurrent alcohol-associated hepatitis (rAH) are sparse. We investigated the incidence, risk factors, and outcomes of rAH.

METHODS: Hospitalized patients with AH from 2010 to 2020 at a large health care system were followed until death/liver transplant, last follow-up, or end of study (December 31, 2021). AH was defined by NIAAA Alcoholic Hepatitis Consortium criteria; rAH was defined a priori as a discrete AH episode >6 months from index AH hospitalization with interim >50% improvement or normalization of total bilirubin. Multivariable competing risk …

Microbial Stimulation Of Oxytocin Release From The Intestinal Epithelium Via Secretin Signaling, Heather A Danhof, Jihwan Lee, Aanchal Thapa, Robert A Britton, Sara C Di Rienzi

Faculty, Staff and Students Publications

Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, …

Predictive Algorithm For Hepatic Steatosis Detection Using Elastography Data In The Veterans Affairs Electronic Health Records, Saroja Bangaru, Ram Sundaresh, Anna Lee, Nicole Prause, Frank Hao, Tien S Dong, Monica Tincopa, George Cholankeril, Nicole E Rich, Jenna Kawamoto, Debika Bhattacharya, Steven B Han, Arpan A Patel, Magda Shaheen, Jihane N Benhammou

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions. Early detection can identify at-risk patients who can be linked to hepatology care. The vibration-controlled transient elastography (VCTE) controlled attenuation parameter (CAP) is biopsy validated to diagnose hepatic steatosis (HS). We aimed to develop a novel clinical predictive algorithm for HS using the CAP score at a Veterans' Affairs hospital.

METHODS: We identified 403 patients in the Greater Los Angeles VA Healthcare System with valid VCTEs during 1/2018-6/2020. Patients with alcohol-associated liver disease, genotype 3 hepatitis C, any malignancies, or liver transplantation were excluded. Linear regression was used …

Risk Stratification Model For Hepatocellular Cancer In Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Jennifer R Kramer, Xian Yu, Yumei Cao, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis.

METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating …

Exposure To Agent Orange And Hepatocellular Carcinoma Among Us Military Personnel, Jihane N Benhammou, Mei Leng, Shailja C Shah, George Cholankeril, Tien S Dong, Arpan A Patel, Myron J Tong

Faculty, Staff and Students Publications

IMPORTANCE: Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers.

OBJECTIVE: To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO …

Unexpected Hepatic Manifestations Of Rheumatoid Arthritis, Ankur Patel, Christo Mathew, Lucas Mcgowan, Sarah Bohac, Andrew Caruso, Scott Larson

Faculty, Staff and Students Publications

Rheumatoid arthritis is an inflammatory condition typically affecting joint spaces. However, extra-articular manifestations are common including vascular and gastrointestinal tract involvement. This disease may also manifest as nodules, although these are typically found in the extremities and are very rarely seen in the liver. When a patient presents with liver nodules, an extensive work-up is typically completed to determine infectious, inflammatory, or malignant etiologies. We report hepatic findings of rheumatoid arthritis during an extensive inpatient investigation of liver lesions.

Gastrointestinal: A Rare Case Of Concurrent Vulvar Crohn's Disease And Pyoderma Gangrenosum, J. Bommireddipally, K. Broussard, H. Osman, A. Uhlhorn, N. Loganantharaj

School of Medicine Faculty Publications

No abstract provided.

Colocolic Fistula: A Rare Consequential Presentation Of Cecal Mucinous Adenocarcinoma, Jessica Rutyna, Paige Stratton, Rutwik Pradeep Sharma, Anthony V. Baratta Jr

Advances in Clinical Medical Research and Healthcare Delivery

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Relative to a 5-year survival rate, CRC patients diagnosed with localized disease accrue a 90% survival rate while those diagnosed with distant-stage disease maintain 14% survival. Mucinous adenocarcinoma (MAC) is a unique subtype of CRC characterized by the presence of extracellular mucin occupying 50% of tumor expansion. Fistula complications of colonic malignancy have rarely been reported and more commonly occur as complications of diverticulitis. Colocolic fistulae are atypical consequences of colon cancer, which have been rarely reported. We wish to report a unique case …

Exploring Alternative Treatment Choices For Multidrug-Resistant Clinical Strains Of Helicobacter Pylori In Mongolia, Ayush Khangai, Batsaikhan Saruuljavkhlan, Dashdorj Azzaya, Boldbaatar Gantuya, Khasag Oyuntsetseg, Junko Akada, Takashi Matsumoto, Yoshio Yamaoka

Faculty, Staff and Students Publications

Helicobacter pylori is a pathogen related to severe diseases such as gastric cancer; because of rising antimicrobial-resistant strains, failure to eradicate H. pylori with antibiotics has increased worldwide. Multidrug-resistant H. pylori and gastric cancer is common in Mongolia; therefore, we aimed to explore alternative antimicrobial treatments and the genomes of resistant strains in this country. A total of 361 H. pylori strains isolated from patients in Mongolia were considered. Minimal inhibitory concentrations for two fluoroquinolones (ciprofloxacin and moxifloxacin), rifabutin, and furazolidone were determined via two-fold agar dilution. Genomic mutations in antibiotic-resistant strains were identified by next-generation sequencing using the Illumina …

Growth Rates And Histopathological Outcomes Of Small (6-9 Mm) Colorectal Polyps Based On Ct Colonography Surveillance And Endoscopic Removal, B Dustin Pooler, David H Kim, Kristina A Matkowskyj, Michael A Newton, Richard B Halberg, William M Grady, Cesare Hassan, Perry J Pickhardt

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: The natural history of small polyps is not well established and rests on limited evidence from barium enema studies decades ago. Patients with one or two small polyps (6-9 mm) at screening CT colonography (CTC) are offered CTC surveillance at 3 years but may elect immediate colonoscopy. This practice allows direct observation of the growth of subcentimetre polyps, with histopathological correlation in patients undergoing subsequent polypectomy.

DESIGN: Of 11 165 asymptomatic patients screened by CTC over a period of 16.4 years, 1067 had one or two 6-9 mm polyps detected (with no polyps ≥10 mm). Of these, …